High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor

There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery.For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data.Eight miRNAs (miRNA-27b, -122, -142–5p, -196a, -223, -590–5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732–153.789; P = 0.015).MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.     

Gastric Carcinomas in Young (Younger than 40 Years) Chinese Patients: Clinicopathology,Family History,and Postresection Survival

Little is known about clinicopathological characteristics of gastric carcinoma (GC) in young (≤40 years) Chinese patients. We aimed in this study to analyze those features along with family history and prognostic factors after resection.We retrospectively reviewed all 4671 GC resections (surgical and endoscopic) performed at our center from 2004 to 2014 and identified 152 (3.2%) consecutive young patients. Patient demographics, clinical results, family history, and endoscopic-pathological findings were analyzed along with the older (>41 years) GC controls recruited in the same study period. Clinicopathological factors related to postresection outcomes were assessed statistically.The trend of GC resections in young patients was not changed over the study period. Compared to old GCs, the young GC cohort was predominant in women, positive family history, middle gastric location, the diffuse histology type, shorter duration of symptoms, and advanced stage (pIII+pIV, 53.3%). Radical resection was carried out in 90.1% (n = 137) with a better 5-year survival rate (70.3%) than palliative surgery (0%, n = 15). There was no significant difference in clinicopathological characteristics between familial GC (FGC, n = 38) and sporadic GC (SGC, n = 114) groups. Very young patients (≤ 30 years, n = 38) showed lower Helicobacter pylori (Hp) infection and significantly higher perineural invasion rates, compared to older (31–40 years) patients. Hp infection was more commonly seen in the Lauren''s intestinal type and early pT stages (T1+T2). Independent prognostic factors for worse outcomes included higher serum CA 72–4, CA 125 levels, positive resection margin, and stage pIII–pIV tumors. The 5-year survival rate was significantly higher in patients with radical resection than those without.GCs in young Chinese patients were prevalent in women with advanced stages but showed no significant differences in clinicopathology between FGC and SGC groups. High serum CA 72–4 and CA 125 levels may help identify patients with worse outcomes. Radical resection improved postresection survival.     

Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from Grade 3 Gastroenteropancreatic Neuroendocrine Tumors

Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare, and there is no report specifically dealing with patients of liver metastases from G3 GEP NETs.From January 2004 to January 2014, 36 conservative patients with G3 GEP NET liver metastases were retrospectively identified from 3 hepatobiliary centers in China. The clinical features and treatment outcomes were analyzed.Aggressive locoregional treatments (LT, including cytoreductive surgery, radiofrequency ablation, and liver-directed intra-arterial intervention) and systemic therapy (ST) were introduced separately or combined, with 26 (72%) patients receiving resection of primary tumor and/or hepatic metastases, 12 patients receiving non-surgical locoregional interventions (NSLRIs), and 22 patients receiving certain kind of STs. Median overall survival (OS) was 20.0 months (95% confidence interval [CI]: 8.9–31.1 months) and survival rates were 62.6%, 30.1%, and 19.8%, at 1, 3, and 5 years, respectively. The median OS was 9.0 months (95%CI: 3.3–14.7 months) for patients receiving only STs (n = 6), 19 months (95%CI: 1.3–36.8 months) for patients receiving LT followed by STs (n = 16), and 101 months (95%CI: 0.0–210.2 months) for patients receiving only LT (n = 12). Moreover, compared with those receiving only ST or best supportive care, patients given certain types of LTs had higher rates of symptom alleviation (3/8 versus 20/23). On univariate analysis, positive prognostic factors of survival were pancreatic primary tumor (P = 0.013), normal total bilirubin level (P = 0.035), receiving surgery (P = 0.034), receiving NSLRI (P = 0.014), and sum of diameters of remnant tumor < 5 cm (P = 0.008). On multivariate analyses, pancreatic primary tumor (P = 0.015), normal total bilirubin level (P = 0.002), and sum of diameters of remnant tumor < 5 cm (P = 0.001) remained to be independent prognostic factors.For patients with G3 GEP NET liver metastases, aggressive LTs may improve clinical outcomes. Larger studies with prospective design are warranted to consolidate these results, and to discover the most appropriate seletion criteria for patients to undergo different kinds of aggressive LTs and to find the most effective combinations, with or without ST.     

Prognostic value of targeted temperature management on outcomes of hanging-induced out-of-hospital cardiac arrest: A nationwide observational study

This study aimed to evaluate the prognostic significance of targeted temperature management (TTM) on hanging-induced out-of-hospital cardiac arrest (OHCA) patients using nationwide data of South Korea.Adult hanging-induced OHCA patients from 2008 to 2018 were included in this nationwide observational study. Patients who assigned into 2 groups based on whether they did (TTM group) or did not (non-TTM group) receive TTM. Outcome measures included survival to hospital discharge and a good neurological outcome at hospital discharge.Among the 293,852 OHCA patients, 3545 patients (non-TTM, n = 2762; TTM, n = 783) were investigated. After propensity score matching for all patients, 783 matched pairs were available for analysis. We observed no significant inter-group differences in the survival to hospital discharge (non-TTM, n = 27 [3.4%] vs TTM, n = 23 [2.9%], P = .666) or good neurological outcomes (non-TTM, n = 23 [2.9%] vs TTM, n = 14 [1.8%], P = .183). In the multivariate analysis, prehospital return of spontaneous circulation (odds ratio [OR], 22.849; 95% confidence interval [CI], 11.479–45.481, P < .001) was associated with an increase in survival to hospital discharge, and age (OR, 0.971; 95% CI, 0.944–0.998, P = .035), heart disease (OR, 16.875; 95% CI, 3.028–94.036, P = .001), and prehospital return of spontaneous circulation (OR, 133.251; 95% CI, 30.512–581.930, P < .001) were significant prognostic factors of good neurological outcome. However, TTM showed no significant association with either outcome.There were no significant differences in the survival to hospital discharge and good neurological outcomes between non-TTM and TTM groups of hanging-induced OHCA patients.     

Single-center experience on actual mid-term (≥5 years) and long-term (≥10 years) survival outcome in patients with hepatocellular carcinoma after curative hepatectomy: A bimodal distribution

Analysis for actual mid-term (≥5 years) and long-term (≥10 years) survivors with hepatocellular carcinoma (HCC) following curative hepatectomy are rarely reported in the literature.This retrospective study aims to study the mid- and long-term survival outcome and associated prognostic factors following curative hepatectomy for HCC in a tertiary referral center.The clinical data of 325 patients who underwent curative hepatectomy for HCC were reviewed. They were stratified into 3 groups for comparison (Group 1, overall survival <5 years; Group 2, overall survival ≥5, and <10 years; Group 3, overall survival ≥10 years). Favorable independent prognostic factors for mid- and long-term survival were analyzed.A bimodal distribution of actual survival outcome was observed, with short-term (<5 years) survival of 52.7% (n = 171), mid-term survival of 18.1% (n = 59), and long-term survival of 29.2% (n = 95). Absence of microvascular invasion (OR 3.690, 95% CI: 1.562–8.695) was independent good prognostic factor for mid-term survival. Regarding long-term overall survival, young age (OR 1.050, 95% CI: 0.920–0.986), ASA grade ≤2 (OR 3.746, 95% CI: 1.325–10.587), high albumin level (OR 1.008, 95% CI: 0.920–0.986), solitary tumor (OR 3.289, 95% CI: 1.149–7.625) and absence of microvascular invasion (OR 4.926, 95% CI: 2.192–11.111) were independent good prognostic factors.Curative hepatectomy results in bimodal actual survival outcome with favorable long-term survival rate of 29.2%. Favorable independent prognostic factors (age, ASA grade, albumin level, tumor number, and microvascular invasion) are identified for overall survival.     

The clinical profiles,management, and prognostic factors of biliary mixed neuroendocrine nonneuroendocrine neoplasms: A systematic review of the literature

Background:Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs.Methods:A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan–Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression.Results:Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time.Conclusion:Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.     

A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin

Carcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients.We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated.The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ≤3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively.In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments.     

An Ultra-Deep Targeted Sequencing Gene Panel Improves the Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma

An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3–4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3–4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in OSCC patients regardless of ECS presence.     

Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer

The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.     

The prognostic value of lncRNA AGAP2-AS1 in cancer patients: A meta-analysis

Background:ArfGAP with GTPase domain, Ankyrin repeat and PH domain 2 Antisense 1 (AGAP2-AS1) is a promising long noncoding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of long noncoding RNA AGAP2-AS1 in cancer patients.Methods:A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases were carried out in this meta-analysis. Synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of AGAP2-AS1 expression in tumors.Results:The final meta-analysis included 10 studies that contained 948 patients. The pooled results provided evidence that AGAP2-AS1 overexpression predicted reduced overall survival (OS) (HR = 1.77, 95% CI: 1.49–2.09, P < .00001), disease-free survival (HR = 1.84, 95% CI: 1.40–2.41, P < .0001), and progression-free survival (HR = 1.84, 95% CI: 1.01–3.33, P = .04) and for various cancers. Additionally, the AGAP2-AS1 overexpression was concerned with lymph node metastasis (positive vs negative, OR = 2.95, 95% CI: 1.96–4.45, P < .00001), advanced tumor node metastasis stage (III/IV vs I/II, OR = 3.73, 95% CI: 2.71–5.13, P < .00001), and tumor size (larger vs smaller, OR = 2.28, 95% CI: 1.24–4.18, P = .008). Besides, data from gene expression profiling interactive analysis dataset verified the results in our meta-analysis. The results showed that the expression level of AGAP2-AS1 was higher in most tumor tissues than in the corresponding normal tissues and was linked to poor OS and disease-free survival.Conclusions:Our results indicated that AGAP2-AS1 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that AGAP2-AS1 might function as a promising predictor for clinical outcomes in cancer.     

Association between Alpha B-crystallin expression and prognosis in patients with solid tumors: A protocol for systematic review and meta-analysis

Background:Alpha B-crystallin (CRYAB), as a small heat shock protein, may play critical roles in the tumorigenesis and progression of several kinds of human cancers. However, the prognostic value of CRYAB in solid malignancies remains controversial. The aim of the present study was to investigate the association between CRYAB expression and clinicopathology and prognosis of solid tumor patients.Methods:PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched to retrieve studies that investigated the prognostic value of CRYAB expression in various solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the strength of association between CRYAB expression and survival in patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to assess the correlation between CRYAB expression and clinicopathological characteristics of patients with solid tumors.Results:A total of 17 studies, including 18 cohorts with 6000 patients, were included in this meta-analysis. Our results showed that increased CRYAB expression could predict poor overall survival (HR = 1.81, 95% CI: 1.50–2.19, P < .001), disease-free survival (HR = 1.47, 95% CI: 1.16–1.86, P = .001), and disease-specific survival (HR = 1.40, 95% CI: 1.19–1.63, P < .001) in patients with cancer. Furthermore, the high expression level of CRYAB was associated with certain phenotypes of tumor aggressiveness, such as lymph node metastasis (OR = 2.46, 95% CI: 1.48–4.11, P = .001), distant metastasis (OR = 3.34, 95% CI: 1.96–5.70, P < .001), advanced clinical stage (OR = 2.24, 95% CI: 1.24–4.08, P = .008), low OS rate (OR = 4.81, 95% CI: 2.82–8.19, P < .001), and high recurrence rate (OR = 1.38, 95% CI: 1.11–1.72, P = .004).Conclusions:CRYAB may serve as a valuable prognostic biomarker and therapeutic target in human solid tumors.     

Prognostic factors of patients after liver cancer surgery: Based on Surveillance,Epidemiology, and End Results database

This study aimed to investigate the prognostic factors of patients after liver cancer surgery and evaluate the predictive power of nomogram. Liver cancer patients with the history of surgery in the Surveillance, Epidemiology, and End Results database between 2000 and 2016 were preliminary retrieved. Patients were divided into the survival group (n = 2120, survival ≥5 years) and the death group (n = 2615, survival < 5 years). Single-factor and multi-factor Cox regression were used for analyzing the risk factors of death in patients with liver cancer after surgery. Compared with single patients, married status was the protective factor for death in patients undergoing liver cancer surgery (HR = 0.757, 95%CI: 0.685–0.837, P < .001); the risk of death in Afro-Americans (HR = 1.300, 95%CI: 1.166–1.449, P < .001) was higher than that in Caucasians, while the occurrence of death in Asians (HR = 0.821, 95%CI: 0.1754–0.895, P < .0012) was lower; female patients had a lower incidence of death (HR = 0.875, 95%CI: 0.809–0.947, P < .001); grade II (HR = 1.167, 95%CI: 1.080–1.262, P < .001), III (HR = 1.580, 95%CI: 1.433–1.744, P < .001), and IV (HR = 1.419, 95%CI: 1.145–1.758, P = 0.001) were the risk factors for death in patients with liver cancer. The prognostic factors of liver cancer patients after surgery include the marital status, race, gender, age, grade of cancer and tumor size. The nomogram with good predictive ability can provide the prediction of 5-year survival for clinical development.     

High expression of HOXB7 is an unfavorable prognostic factor for solid malignancies: A meta-analysis

Background:HOXB7 is abnormally expressed in a variety of tumors, but its prognostic value remains unclear due to sample size limitation and outcome inconsistency in previous studies. This meta-analysis was performed to explore the effect of HOXB7 expression on prognoses and clinicopathological factors in range of the whole solid tumors.Methods:PubMed, EMBASE, and Web of Science databases were searched to identify included studies. Hazard ratios (HR) with its 95% confidence interval (CI) and clinicopathological factors were extracted. Subgroup analyses were performed according to histopathological type, tumor occurrence systems, and HOXB7 detection methods.Results:A total of 3430 solid tumors patients from 20 studies (21 cohorts) were included in the meta-analysis. The results showed that high HOXB7 expression was significantly associated with worse survival (overall survival: HR = 1.98, 95%CI: 1.74–2.26, P < .001 and disease-free survival: HR = 1.59, 95%CI: 1.21–2.09, P = .001), more advanced tumor-node-metastasis (TNM) stage (odds ratio [OR] = 2.14, 95%CI: 1.68–2.73, P < .001), positive lymph node metastasis (OR = 2.16, 95%CI: 1.74–2.70, P < .001), more distant metastasis (OR = 1.63, 95%CI: 1.01–2.63, P = .048), poorer differentiation (OR = 1.48, 95%CI: 1.14–1.91, P = .003), and higher Ki-67 expression (OR = 2.53, 95%CI: 1.68–3.84, P < .001). Subgroup analysis showed that survival of patients with HOXB7 high expression was worse in either squamous cell carcinomas or non-squamous cell carcinomas, digestive tumors or non-digestive tumors, and protein level or mRNA level.Conclusion:High HOXB7 expression might be a valuable biomarker of poor prognosis for solid tumors. HOXB7 promotes tumor proliferation and metastasis, and is associated with poorer differentiation, more advanced stage, even the chemotherapy resistance, suggesting that HOXB7 is a potential therapeutic target for solid tumors.     

Human Papillomavirus Infections are Common and Predict Mortality in a Retrospective Cohort Study of Taiwanese Patients With Oral Cavity Cancer

Human papillomavirus (HPV) infections are deemed to play a role in the pathogenesis of oral cavity cancer (OCC). However, their exact prevalence and clinical significance remain unclear. Herein, we investigated the prevalence and prognostic value of HPV infections in a large sample of Taiwanese OCC patients.This study was designed as a retrospective cohort study. Between 2004 and 2011, we identified 1002 consecutive patients with newly diagnosed OCC who were scheduled for standard treatment. HPV genotyping was performed in tumor specimens using polymerase chain reaction-based HPV blots. To investigate the temporal trends of HPV infections and their impact on 5-year overall survival (OS), patients were divided into 2 cohorts according to calendar periods: “2004 cohort” (2004–2007; n = 466) and “2008 cohort” (2008–2011; n = 536). Univariate and multivariate Cox regression models were also used to identify the independent predictors of OS in the 2 cohorts. A weighted risk score was assigned to each factor based on the range of their corresponding hazard ratios and validated in both cohorts using the c-statistic.The overall prevalence of HPV infections was 19%, with a trend toward decreasing rates from 2004 to 2011. In patients without risky oral habits, the 5-year OS rate of HPV-positive patients was significantly lower than that of HPV-negative cases (49% vs 80%; P = 0.021). In the 2004 cohort, multivariate analysis identified HPV16, pathological T3/T4, pathological N1/N2, and extracapsular spread as independent adverse prognostic factors for OS. In the 2008 cohort, pathological N1/N2, pathological stage III/IV, and histological tumor depth >8 mm were identified as independent adverse prognostic factors. Using a weighted grading system incorporating HPV16 infection, we devised a prognostic index that identified 4 distinct risk categories with 5-year OS rates ranging from 25% to 89% (c-statistic = 0.76) in the 2004 cohort. The validity of the index was internally confirmed in the 2008 cohort (c-statistic = 0.71).We conclude that HPV infections are common in Taiwanese OCC patients and predict 5-year OS. If independently validated, our composite prognostic score comprising HPV16 infection may be useful for allocating OCC patients to risk-adapted therapies.     

Prognostic role of tripartite motif containing 24 in various human solid malignant neoplasms: An updated meta-analysis and systematic review

Background:Currently, clinical studies of tripartite motif containing 24 (TRIM24) on human solid malignant neoplasms were developing, but the prognosis value of TRIM24 continues to be controversial. The aim of our study is to explore the prognostic effect of TRIM24 in various human solid malignant neoplasms.Methods:We performed a comprehensive research for eligible studies which evaluated the prognostic roles of TRIM24 in cancer patients based on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The hazard ratios (HRs) with 95% confidence intervals (CIs) for various malignances were extracted from eligible studies.Results:A total of 13 studies with 1909 patients were enrolled in this analysis. Combined analyses showed that high expression of TRIM24 significantly predicted poorer overall survival both in univariate analysis (HR = 1.61, 95% CI 1.21–2.15, P = .001) and multivariate analysis (HR = 2.19, 95% CI 1.10–4.38, P = .026). In stratified analyses, high TRIM24 expression level predicted even worse overall survival in hormone-related cancers (HR = 1.92, 95% CI 1.28–2.86, P = .001). Although, expression of TRIM24 failed to show a significant relation with progression-free survival/disease-free survival/recurrence-free survival (HR = 1.42, 95% CI 0.93–2.16, P = .106), high expression predicted significant worse progression-free survival/disease-free survival/recurrence-free survival in hormone-related cancer (HR = 1.71, 95% CI 1.12–2.59, P = .013).Conclusion:TRIM24 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients especially for patients with hormone-related malignancies.     

Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study

Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973–2011), and Linköping Cancer (LC, 1972–2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057–1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493–10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106–1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.     

Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer

To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were enrolled. Overall survival (OS) and disease-free survival (DFS) were evaluated over a 10-year follow-up. PGK1 expression was assessed by tissue microarray and immunohistochemistry. Prognostic significance was analyzed using multivariate Cox regression.PGK1 was highly expressed in all gallbladder mucosa. Decreased PGK1 expression was detected in 54.7% (52/95) of patients with GBC. It was significantly down-regulated in GBC samples compared with that in gallbladder mucosa (P < 0.0001), and was associated with multiple clinicopathological factors. Multivariate survival analysis showed that low PGK1 expression was associated with shorter OS (median 12.8 vs 45.4 months; hazard ratio [HR] = 3.077; 95% confidence interval [CI], 1.373–6.897; P = 0.006) and DFS (median 8.3 vs 37.9 months; HR = 2.988; 95% CI, 1.315–6.790; P = 0.009), indicating that PGK1 expression was an independent prognostic factor in patients with GBC.Low PGK1 expression was associated with progression in patients with GBC. PGK1 expression could be a useful prognostic biomarker for GBC.     

Prognostic Value of Lymph Node Ratio in Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiotherapy Followed by Total Mesorectal Excision

Although the absolute number of positive lymph nodes (LNs) has been established as 1 of the most important prognostic factors in rectal cancers, many researchers have proposed that the lymph node ratio (LNR) may have better predicted outcomes. We conducted a retrospective study to compare the predictive ability of LNR and ypN category in rectal cancer.A total of 264 locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) between 2005 and 2012 were reviewed. All patients were categorized into 3 groups or patients with metastatic LNs were categorized into 2 groups according to the LNR. The prognostic effect on overall survival (OS) and disease-free survival (DFS) was evaluated.With a median follow-up of 45 months, the OS and DFS were 68.4% and 59.3% for the entire cohort, respectively. The respective 5-year OS and DFS rates for the 3 groups (LNR = 0, 0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were as follows: 83.2%, 72.6%, and 49.4% (P < 0.001) and 79.5%, 57.3%, and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that LNR and differentiation, but not the number of positive LNs, had independent prognostic value for OS (hazard ratio [HR] = 2.328, 95% confidence interval [CI]: 1.850–4.526, P < 0.001) and DFS (HR = 3.004, 95% CI: 1.616–5.980, P < 0.001). As for patients with positive LNs, the respective 5-year OS and DFS rates for the 2 groups (0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were 72.6% and 49.4% (P < 0.001) and 57.3% and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that only LNR was an independent factor for OS (HR = 3.214, 95% CI: 1.726–5.986, P < 0.001) and DFS (HR = 4.230, 95% CI: 1.825–6.458, P < 0.001). Subgroups analysis demonstrated that the ypN category had no impact on survival whereas increased LNR was a significantly prognostic indicator for worse survival in the LNs < 12 subgroup.LNR is an independent prognostic factor in LARC patients treated with preoperative CRT followed by TME. It may be a better independent staging method than the number of metastatic LNs when <12 LNs are harvested after preoperative CRT.     

Pretreatment Serum Lactate Dehydrogenase and N Classification Predict Long-Term Survival and Distant Metastasis in Patients With Nasopharyngeal Carcinoma Who Have A Positive Family History of Cancer

The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer.Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models.The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13–9.74, P < 0.0001) and elevated pretreatment serum LDH (HR 2.87, 95% CI 1.08–7.62, P = 0.034) were independent prognosticators for OS. Female patients (HR 0.42, 95% CI 0.19–0.95, P = 0.037) and patients with normal pretreatment serum LDH (HR 2.42, 95% CI 1.02–5.78, P = 0.046) had better DMFS.Elevated pretreatment serum LDH and N classification are independent prognostic factors for poorer survival in patients with NPC who have a positive FH of cancer.     

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis

Background:There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods:Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I²-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results:Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76–6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01–1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01–1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22–2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20–1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32–4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the “Publication year”, “Country”, “Sample size”, and “Cutoff value” might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.