Lymph node ratio,an independent prognostic factor for patients with stage II-III rectal carcinoma

BackgroundIdentification of the proper surgical method and the most reliable prognostic parameters of rectal carcinomas is a challenging issue. The aim of this paper was to determine the possible prognostic role of the number of harvested lymph nodes versus lymph node ratio (LNR) in patients with rectal carcinomas, and the proper value of LNR that can be used as prognostic parameter.Materials and methodsA retrospective study was performed in 186 consecutive patients with rectal carcinomas that underwent surgical resection. The LNR was calculated for cases from stage II-III, and was correlated with classic prognostic parameters and overall survival (OS).ResultsA statistically significant difference was found between LNR of 0.15 and OS (p = 0.03), respectively LNR > 0.15 and TNM stage (p < 0.0001), but also tumor infiltration level (p < 0.05). The number of harvested lymph nodes was not correlated with the tumor stage (r = 0.148, p = 0.06) and this parameter did not influence the OS, when the number of 12 or 14 lymph nodes was used as the ideal value (p = 0.6 and p = 0.66, respectively).ConclusionIn patients with rectal carcinomas that underwent preoperative chemoradiotherapy, a LNR of 0.15 is a parameter with independent prognostic value, comparing with the number of harvested lymph nodes. The specific LNR should be calculated in larger cohorts.     

Comparison of abdominal and minimally invasive radical hysterectomy in patients with early stage cervical cancer

Purpose: The aim of this study was to compare survival outcomes of open radical hysterectomy and minimally invasive radical hysterectomy (MIS) in early stage cervical cancer.Methods: A retrospective analysis of 148 patients with stage IB1 - IIA2 cervical cancer who underwent either minimally invasive or open radical hysterectomy. Tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS) were compared according to surgical approach.Results: In total, 110 and 38 patients were assigned to open surgery and MIS groups. After a medical follow-up of 42.1 months, the groups showed similar survival outcomes (recurrence rate, DFS, and OS). However, in patients with tumor size >2 cm, recurrence rate was significantly higher in MIS group (22.5% vs 0%; p=0.008). And in patients with tumor size >2 cm, MIS group showed significantly poorer DFS than open surgery group (p=0.017), although OS was similar between the two groups (p=0.252).Conclusion: In patients with tumor size >2 cm, MIS was associated with higher recurrence rates and poorer DFS than open surgery. However, in patients with tumor size ≤2 cm, MIS did not seem to compromise oncologic outcomes.     

Towards standardization of lymph-node ratio classifications: Validation and comparison of different lymph node ratio classifications for predicting prognosis of patients with resected gastric cancer

IntroductionThe TNM staging system is the main prognostic tool for GC, but the number of metastatic lymph nodes (LN) can be affected by surgical, pathological, tumor or host factors. Several authors have shown that lymph node ratio (LNR) may be superior to TNM staging in GC. However, cut-off values vary between studies and LNR assessment is not standardized.Material and methodsRetrospective study of all GC resected in a western tertiary center (N = 377). Clinical features were collected and pathological features were assessed by two independent pathologists. Eight LNR classifications were selected and applied to our patients. Statistical analyses were performed.Results315 patients were included. Most tumors were T3 (49.2%) N+ (59.3%). During follow-up, 36.7% of patients progressed and 27.4% died due to tumor. All LNR classifications were significantly associated with clinicopathological features such as Laurén subtype, lymphovascular invasion, perineural infiltration, T stage, tumor progression or death. All LNR classifications were independent prognostic factors for OS and DFS, and ROC analyses calculated similar AUC values for all staging systems. Kaplan-Meier curves showed that Pedrazzani, Wang, Liu and Huang classifications stratified patients better into three (Pedrazzani) or four categories. These classifications tended to downstage TNM N2 and N3 tumors. In cases with less than 16 LNs resected, Pedrazzani and Wang classifications showed the best prognostic performance.ConclusionsPedrazzani, Wang, Liu and Huang classifications showed good prognostic performance in western GC patients. Larger studies in other cohorts are needed to identify the most consistent LNR classification for GC.     

CD105- and CD31-assessed microvessel density in laryngeal carcinoma biopsies as a predictor of recurrence after exclusive primary surgery

PurposeSurgery is currently indicated as a unimodal therapeutic approach with curative intent in selected laryngeal squamous cell carcinomas (LSCCs) ranging from stage I to III. The main aim of this study was to evaluate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in biopsy and in surgical specimens from a cohort of consecutive stage I-III LSCCs who had undergone exclusive primary surgery, according to current guidelines.Materials and methodsCD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 24 consecutive cases of LSCC who underwent exclusive surgery.ResultsOn biopsy specimens, CD105- and CD31-assessed MVD were positively associated with recurrence risk (hazard ratio [HR] 1.266, p = 0.0034 and HR 1.265, p = 0.0081, respectively). In surgical specimens, CD105- and CD31-assessed MVD were significantly associated with disease-free survival (DFS) (HR 1.213, p = 0.0016 and HR 1.237, p = 0.0023 respectively). Considering a stratification based on median value, recurrence risk was higher in patients with a CD105-assessed MVD>0 in both biopsies and surgical specimens (HR 11.005, p = 0.0326 and HR 34.483, p = 0.0311). No significant differences in terms of recurrence risk were found for CD31-assessed on biopsies or on surgical specimens.ConclusionsThis study supports the role of biopsy CD105-MVD as a predictor of recurrence after exclusive surgery for LSCCs. Further prospective studies are mandatory to better characterize the prognostic role of CD105-MVD evaluated on biopsies to develop novel criteria to identify patients at higher risk of recurrence for more aggressive approaches or adjuvant treatment.     

Sarcopenia as a Predictor of Prognosis in Early Stage Ovarian Cancer

BackgroundTo identify sarcopenia as a predictive prognostic factor of ovarian cancer in terms of survival outcome in patients with early-stage ovarian cancer.MethodsData of Konkuk University Medical Center from March 2002 to December 2017 were reviewed retrospectively. Eighty-two patients who underwent surgery due to early-stage (International Federation of Gynecology and Obstetrics stage I/II) ovarian cancer and had computed tomography (CT) images taken at the initial diagnosis were included. The initial CT scan images were analyzed with SliceOmatic software (TomoVision). A sarcopenia cutoff value was defined as a skeletal muscle index of ≤ 38.7 cm²/m². Overall survival (OS) times were compared according to the existence of sarcopenia, and subgroup analyses were performed.ResultsA Kaplan-Meier analysis showed a significant survival disadvantage for patients with early-stage ovarian cancer when they had sarcopenia (P < 0.001; log-rank test). Sarcopenia remained a significant prognostic factor for OS in early-stage ovarian cancer, in a Cox proportional hazards model regression analysis (HR, 21.9; 95% CI, 2.0–199.9; P = 0.006).ConclusionThis study demonstrated that sarcopenia was predictive of OS in patients with early-stage ovarian cancer. Further prospective studies with a larger number of patients are warranted to determine the extent to which sarcopenia can be used as a prognostic factor in ovarian cancer.     

Development of a simplified tumor-lymph node ratio classification system for patients with resected gastric cancer: A western study

IntroductionGastric cancer (GC) shows high recurrence and mortality rates. The AJCC TNM staging system is the best prognostic predictor, but lymph node assessment is a major source of controversy. Recent studies have found that lymph node ratio (LNR) may overcome TNM limitations. Our aim is to develop a simplified tumor-LNR (T-LNR) classification for predicting prognosis of resected GC.MethodsRetrospective study of all GC resected in a tertiary center in Spain (N = 377). Clinicopathological features were assessed, LNR was classified into N0:0%, N1:1–25%, N2:>25%, and a T-LNR classification was developed. Statistical analyses were performed.Results317 patients were finally included. Most patients were male (54.6%) and mean age was 72 years. Tumors were intestinal (61%), diffuse (30.8%) or mixed (8.1%). During follow-up, 36.7% and 27.4% of patients progressed and died, respectively. T-LNR classification divided patients into five prognostic categories (S1-S5). Most cases were S1-S4 (26.2%, 19.9%, 22.6% and 23.6%, respectively). 7.6% of tumors were S5. T-LNR classification was significantly associated with tumor size, depth, macroscopical type, Laurén subtype, signet ring cells, histologic grade, lymphovascular invasion, perineural infiltration, infiltrative growth, patient progression and death. Kaplan-Meier curves for OS showed an excellent patient stratification with evenly spaced curves. As for DFS, T-LNR classification also showed good discriminatory ability with non-overlapping curves. T-LNR classification was independently related to both OS and DFS.ConclusionsT-LNR classifications can successfully predict prognosis of GC patients. Larger studies in other geographic regions should be performed to refine this classification and to validate its prognostic relevance.     

Prognostic value of CD133 expression in stage I lung adenocarcinomas

CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.     

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis.MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis.ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019).ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.     

Prognostic impact of lncRNA-ATB expression in malignant solid tumors: A meta-analysis

PurposeNumerous studies have reported the prognostic role of lncRNA-ATB high expression in solid tumours, but its prognostic effect is still uncertain. Therefore, the purpose of this meta-analysis was to further comprehensively verify the prognostic role of the lncRNA-ATB high expression in solid tumours.MethodsA literature search was performed using the electronic platforms to obtain relevant research studies published up to 31 May 2019. Confidence intervals of research endpoints in each study were extracted and merged. All data analysis was performed using Stata12.0 software.ResultsA total of 2120 patients with solid cancers in 14 studies were enrolled in our meta-analysis eventually. The analysis results revealed that high expression of lncRNA-ATB was related to lower OS (HR:1.46, P < 0.001), shorter DFS(HR:1.73, P < 0.001), and earlier RFS (HR:2.67, P < 0.001). Besides, the high expression of lncRNA-ATB has a considerable risk of lymph node metastasis (OR:2.13, P = 0.017)and perineural invasion (OR:1.58, P = 0.018).ConclusionsMeta-analysis showed that the high lncRNA-ATB expression was a poor prognostic marker in multiple cancer types. The high expression of lncRNA-ATB symbolizes the high risk of lymph node metastasis and perineural invasion in cancer patients.     

Prognostic Inflammation Score in Surgical Patients with Colorectal Cancer

Several inflammatory markers have been investigated as prognostic parameters in a variety of cancer population with mostly favorable results. This study aimed to verify the significance of common inflammatory markers as prognostic variables and assess whether a selective combination of them as prognostic inflammation score (PIS) could further improve their prognostic values in surgical patients with colorectal cancer (CRC). A total of 265 patients who had undergone curative resection of CRC were reviewed retrospectively. Preoperative levels of inflammatory markers such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and neutrophil/lymphocyte ratio (NLR) were assessed by uni- and multivariate survival analysis with disease-free (DFS) and disease-specific survival (DSS). PIS was constructed with a selective combination of inflammatory markers which were independently significant. On univariate analysis, CRP, ESR, and NLR were significantly associated with DFS and DSS. On multivariate analysis, CRP and NLR were independently significant prognostic variables for DSS and DFS respectively (P=0.013, P=0.021). When PIS was constructed with combination of CRP and NLR, it was independently and significantly associated with both DFS and DSS (P=0.006, P=0.010). Furthermore, PIS was superior to CRP for DSS (HR=15.679 vs. HR=5.183), and NLR for DFS in terms of prognosticating power (HR=4.894 vs. HR=2.687). When PIS is constructed with combination of CRP and NLR, it is a potentially significant prognostic variable associated with poor survival regardless pathologic prognostic variables in patients with CRC after curative resection.     

Decreased expression of lncRNA loc285194 as an independent prognostic marker in cancer: A systematic review and meta-analysis

BackgroundSeveral studies have indicated that lncRNA loc285194 is aberrantly expressed in many types of cancer. This meta-analysis was performed to elucidate the potential role of lncRNA loc285194 as a prognostic marker in malignant tumors.MethodsAn electronic search of PubMed, Medline, Embase, and Web of Science was performed to identify all eligible papers related to the prognostic impact of lncRNA loc285194 expression in cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted from the included studies to explore the association between lncRNA loc285194 expression and patient overall and disease-free survival (OS & DFS). The odds ratios (ORs) were also calculated to assess the association between lncRNA loc285194 expression and clinicopathological parameters.ResultsA total of 14 eligible articles with 1215 patients were included in this meta-analysis. Meta-results revealed that low expression of lncRNA loc285194 was significantly correlated with poorer overall survival (OS; HR = 2.34; 95% CI, 1.78–3.06; P < 0.001) and disease-free survival (DFS; HR = 2.66; 95% CI, 1.95–3.64; P = 0.001) rates in cancer patients. Low lncRNA loc285194 expression was also found to be significantly associated with lymph node metastasis (LNM; OR = 2.17; 95% CI, 1.23–3.83; P = 0.007), and distant metastasis (DM; OR = 2.49; 95% CI, 1.26–4.91; P = 0.009).ConclusionsThis study demonstrated that decreased level of lncRNA loc285194 was associated with poor clinical outcomes for patients with different types of cancer, supporting a promising potential biomarker for prognosis and metastasis in human cancers.     

Long-Term Safety and Efficacy of Prolonged Dual Antiplatelet Therapy according to Baseline Anemia after Percutaneous Coronary Intervention

PurposeWe aimed to evaluate the outcomes of prolonged dual antiplatelet therapy (DAPT) depending on baseline anemia after percutaneous coronary intervention (PCI).Materials and MethodsAmong the 1470 study participants, 448 (30.5%) were classified as having baseline anemia. We categorized the study population according to baseline anemia and DAPT duration: ≤12-month (m) DAPT (n=226) vs. >12-m DAPT (n=222) in anemic patients, and ≤12-m DAPT (n=521) vs. >12-m DAPT (n=501) in non-anemic patients.ResultsDuring a follow-up of 80.8 (interquartile range 60.6–97.1) months, anemic patients showed a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) (26.9% vs. 17.1%, p<0.001) and major bleeding (9.8% vs. 5.1%, p=0.006). Among the non-anemic patients, prolonged DAPT was associated with a reduced rate of MACCEs [inverse probability of treatment weighting (IPTW) adjusted hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.63–0.96; p=0.019] without an increase in major bleeding (IPTW adjusted HR, 1.12; 95% CI, 0.75–1.68; p=0.574). However, prolonged DAPT was not related to the incidence of MACCEs (IPTW adjusted HR, 1.11; 95% CI, 0.88–1.39; p=0.387), with increased major bleeding (IPTW adjusted HR, 2.01; 95% CI, 1.32–3.06; p=0.001) among anemic patients.ConclusionAlthough extended DAPT led to a reduction in MACCEs in non-anemic patients, it was related to increased major bleeding without reducing MACCEs in anemic patients.     

Comparative Survival Outcome of Robot-Assisted Staging Surgery Using Three Robotic Arms versus Open Surgery for Endometrial Cancer

PurposeThere is lack of data on direct comparison of survival outcomes between open surgery and robot-assisted staging surgery (RSS) using three robotic arms for endometrial cancer. The purpose of this study was to compare the overall survival (OS) and disease-free survival (DFS) between open surgery and RSS using three robotic arms for endometrial cancer.Materials and MethodsConsecutive women with endometrial cancer who underwent surgery between May 2006 and May 2018 were identified. Robotic procedures were performed using the da Vinci robotic system, and the robotic approach consisted of three robotic arms including a camera arm. Propensity score matching, as well as univariate and multivariate Cox regression of OS and DFS were performed according to clinicopathologic data and surgical method.ResultsThe study cohort included 423 unselected patients with endometrial cancer, of whom 218 underwent open surgery and 205 underwent RSS using three robotic arms. Propensity score-matched cohorts of 146 women in each surgical group showed no significant differences in survival: 5-year OS of 91% vs. 92% and DFS of 86% vs. 89% in the open and robotic cohorts, respectively (hazard ratio, 1.02; 95% confidence interval, 0.82–1.67). In the univariate analysis with OS as the endpoint, surgical method, age, stage, type II histology, grade, and lymph node metastasis were independently associated with survival. Surgical stage, grade, and type II histology were found to be significant independent predictors for OS in the multivariate analysis.ConclusionRSS using three robotic arms and laparotomy for endometrial carcinoma had comparable survival outcomes.     

Survivin expression is an independent poor prognostic marker in lung adenocarcinoma but not in squamous cell carcinoma

Survivin is a member of the inhibitors of apoptosis and frequently overexpressed in various cancer cells. Overexpression of survivin in lung cancer cells attenuates antitumor effect of tyrosine kinase inhibitors. However, data from the previous studies on the clinicopathologic implication of survivin in non-small-cell lung carcinoma (NSCLC) are inconsistent. We investigated the expression of survivin in 373 cases of surgically resected NSCLC. Correlations between the expression of survivin and clinicopathologic, molecular features and prognostic significance were analyzed. In adenocarcinoma, the increased expression of survivin was associated with the presence of vascular invasion, lymph node metastasis, and tumor recurrences, but we didn’t find any correlation with survivin expression and clinicopathological parameters in squamous cell carcinoma. Patients with high survivin expression had significantly shorter disease-free survival (DFS; 42.2 vs. 58.8 months; p?=?0.001) and shorter overall survival (OS; 60.8 vs. 71.5 months; p?=?0.009) than those with low survivin expression group in adenocarcinoma. In squamous cell carcinoma, the expression of survivin was not associated with prognosis of the patients (DFS; 48.9 vs. 48.7 months; p?=?0.837, OS; 61.0 vs. 62.4 months; p?=?0.771). Multivariate analysis confirmed that survivin was an independent poor prognostic factor in adenocarcinoma (DFS: hazard ratio (HR), 1.687; 95 % confidence interval (CI), 1.123–2.532; p?=?0.012; OS: HR, 1.965; 95 % CI, 1.108–3.486; p?=?0.021). There was no statistically significant difference in the expression of survivin among different molecular subgroups (p?>?0.05). Our results suggest that survivin is an independent negative prognostic factor in adenocarcinoma, but not in squamous cell carcinoma. The different prognostic roles played by survivin in adenocarcinoma and squamous cell carcinoma highlights the biological differences between these two histologic types.     

Maspin expression and anti-apoptotic pathway regulation by bcl2 in laryngeal cancer

ObjectivesComprehension of the interplay of pro-apoptotic and anti-apoptotic stimuli in laryngeal squamous cell carcinoma (LSCC) is crucial to understand tumor development, biological behavior and treatment response. Bcl-2 family proteins mainly regulate the apoptotic signal cascade. In some cancers, maspin seems to influence the balance between pro-apoptosis and anti-apoptosis bcl-2 family proteins. The aim of this study was to investigate the potential relationship between bcl-2 anti-apoptotic factor and the tumor suppressor maspin in LSCC.Materials and methods31 consecutive patients who underwent primary surgery and post-operative radiotherapy for LSCC were evaluated retrospectively. For each case, immunohistochemistry assays for bcl-2 and maspin were performed. Data were also collected on N-status, pT stage, grading, recurrence and disease-free survival (DFS).ResultsPatients with nuclear maspin pattern of expression showed a significantly lower recurrence rate (p = 0.04) and longer DFS (p = 0.0018). The expression of bcl-2 was not associated with recurrence rate or DFS either in the whole cohort or in cases with nuclear maspin pattern, while in patients with non-nuclear maspin pattern, a statistical trend was found toward a shorter DFS for bcl-2 positive cases (p = 0.062). In the multivariate model, only maspin expression pattern retained its independent prognostic significance (p = 0.006).ConclusionsNuclear maspin pattern seemed to be an independent positive prognostic factor, while bcl-2 prognostic value was related to maspin expression pattern. Further investigations are needed to support the use of bcl-2 inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.     

The prognostic value of USP7 and p53 in advanced hypopharyngeal carcinoma

BackgroundHypopharyngeal squamous cell carcinoma (HPSCC) is a rare malignancy of poor prognosis in head and neck. The aim of the study is to assess the expression and prognostic value of USP7 and p53 in advanced HPSCC.MethodsA retrospective study was performed on a cohort of 103 patients with advanced HPSCC. The immunohistochemical expression of USP7 and p53 was evaluated in all the patients, and the prognostic value of USP7 and p53 was further evaluated. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional recurrence-free survival (LRFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis.ResultsIn our study, 78 patients (75.7%) showed low expression of USP7, and the other 25 patients (24.3%) had high expression of USP7; additionally, high USP7 expression was associated with advanced T stage. Low expression of p53 was found in 52 patients (50.5%), while the other 51 patients (49.5%) had a high expression of p53. Our data revealed that low expression of p53 was associated with the advanced N stage (p=0.028). Kaplan–Meier analysis revealed that high expression of USP7 was significantly correlated with the inferior OS, DFS, DMFS, and LRFS, respectively (all p<0.05); additionally, high expression of p53 was correlated with superior OS (p=0.023). The Cox proportional multivariate hazard model revealed that high expression of USP7 was an independent predictor of poor OS, DFS, and LRFS, respectively (all p<0.05).ConclusionsOur findings suggest that USP7 combined with p53 are reliable prognostic factors in patients with advanced HPSCC.     

S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer

Purpose: The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. Methods: Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). Results: Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P = 0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P = 0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P = 0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P = 0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P = 0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P = 0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P = 0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P = 0.013). Conclusions: The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.     

The role of gender in patients with diffuse large B cell lymphoma treated with rituximab-containing regimens: a meta-analysis

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Although gender has not been included in prognostic systems, male gender has been found as a bad prognostic indicator in Hodgkin lymphoma, follicular lymphoma and chronic lymphocytic leukemia. The relationship between gender and prognosis is not clear in patients with DLBCL treated with rituximab-containing regimens. The aim of this meta-analysis is to determine the prognostic/predictive role of gender in patients with DLBCL treated with rituximab-containing regimens.

Material and methods

We systematically searched for studies investigating the relationships between gender and prognosis in DLBCL treated with rituximab-containing regimens. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival, disease-free survival (DFS) and event-free survival (EFS).

Results

A total of 5635 patients from 20 studies were included in the analysis. Our results showed that male gender was associated with poor prognosis in terms of overall survival (OS) (hazard ratio (HR) = 1.155; 95% confidence interval (CI): 1.037–1.286; p < 0.009). The pooled hazard ratio for DFS and EFS showed that male gender was not statistically significant (HR = 1.219; 95% CI: 0.782–1.899; p = 0.382, HR = 0.809; 95% CI: 0.577–1.133; p = 0.217).

Conclusions

The present meta-analysis indicated male gender to be associated with a poor prognosis in patients with DLBCL treated with rituximab-containing regimens.     

Clinical usefulness of gastric adenocarcinoma predictive long intergenic noncoding RNA in human malignancies: A meta-analysis

BackgroundGastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC), a newly identified lincRNA, was reported to be aberrantly expressed in several kinds of cancers and played an important role in tumor progression. This study was performed to systematically estimate the prognostic role of GAPLINC expression in cancer patients.MethodsSeveral electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for potential literature (updated to September 3, 2018). The pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a fixed effects model using Stata12.0 software.ResultsThe pooled results indicated that elevated GAPLINC was significantly related to shorter overall survival (OS) (HR = 1.66, 95%CI: 1.40–1.93, p < 0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Furthermore, high GAPLINC expression was correlated with higher tumor grade (OR = 1.91, 95%CI: 1.35–2.70, p < 0.001), positive lymph node metastasis (OR = 2.80, 95%CI: 1.69–4.64, p < 0.001), deeper infiltration depth (OR = 2.44, 95%CI: 1.43–4.17, p = 0.001) and advanced clinical stage (OR = 3.54, 95%CI: 2.13–5.88, p < 0.001).ConclusionsOur results suggest that elevated GAPLINC was associated with poor clinical outcomes and might serve as a promising prognostic biomarker in cancer survivors.     

Prognostic role of Amphiregulin and the correlation with androgen receptor in invasive breast cancer

BackgroundIn androgen-sensitive prostate cancer, androgenic stimulation induces the synthesis of amphiregulin (AREG). Research is lacking on the role of AREG in invasive breast cancer and the co-expression with androgen receptor (AR) status.Materials and methodsThe present study investigated the prognostic role of AREG in invasive breast cancer cases (N = 298) and the co-expression with the AR status as analysed by immunohistochemistry (IHC).ResultsThe samples were divided into groups according to AREG expression levels: low/no expression (AREG^low/no) and high expression (AREG^high). As shown by cytoplasmic immunostaining, 46.0% (137/298) of invasive breast cancers were AREG^high, and 54.0% (161/298) of cases were AREG^low/no. Co-expression of the AR and AREG accounted for 62.4% (186/298) of cases. A Kaplan–Meier analysis revealed that AREG^high and AR⁺/AREG^high decreased patients’ overall survival (OS) (P = 0.002 and P = 0.006, respectively) and disease-free survival (DFS) (P < 0.001 and P < 0.001, respectively). In Cox models, AR⁺/AREG^high remained an independent prognostic indicator of OS and DFS in invasive breast cancer (hazard ratio [HR], 0.591, 95% confidence interval [CI], 0.407-0.859, P = 0.006; HR, 0.449, 95% CI, 0.236-0.853, P = 0.014, respectively). AREG^high remained an independent prognostic indicator of OS and DFS in estrogen receptor (ER)-negative tumours (P < 0.05).ConclusionsThis study suggested that AREG and the AR were co-expressed in invasive breast cancer. Thus, AREG and the AR may be valuable prognostic biomarkers in invasive breast cancer and promising therapeutic targets, especially in ER-negative breast cancer.