Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma

It has been well accepted that p53 overexpression is associated with advanced stages of cancer. However, the prognostic role of p53 overexpression in esophageal squamous cell carcinoma (ESCC) remains unclear. To investigate the prognostic role of p53 overexpression in patients with ESCC, a retrospective cohort study of 136 ESCC patients was carried out. The expression of p53 protein in tumor tissues was investigated immunohistochemically. Positive expression of p53 protein was detected in 57 ESCC patients (41.9%). The p53 overexpression was associated with smoking (P < 0.001), tumor differentiation (P < 0.001), and tumor size (P < 0.001). In the Kaplan-Meier analysis, patients with p53 overexpression had significantly shorter overall survival than those patients with negative p53 expression (log-rank P < 0.001). Multivariable analysis by Cox regression model further showed that p53 overexpression was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 1.91; 95% confidence interval [95% CI] 1.03-3.54, P = 0.04). Thus, p53 overexpression is associated with poor prognosis in patients with early stage esophageal squamous cell carcinoma, and it’s a significantly independent predictor of poorer overall survival.     

Increased expression of HMGB3: a novel independent prognostic marker of worse outcome in patients with esophageal squamous cell carcinoma

HMGB3, an X-linked member of the high-mobility group (HMG) superfamily of HMG proteins, has been shown to affect numerous tumorigenic progression. However, the expression and the prognostic role of HMGB3 in esophageal squamous cell carcinoma (ESCC) remained unknown. In this study, we examined the HMGB3 expression in ESCC tissues and adjacent nontumorous tissues by qRT-PCR and immuohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. The mRNA levels of HMGB3 were found to be significantly higher in tumorous tissues than in the adjacent normal tissues. We found that the HMGB3 expression was higher in tumorous tissues than in the adjacent non-tumorous tissues by immunohistochemical analysis of paired tissue specimens (P < 0.001). Moreover, there was a significant correlation between HMGB3 expression and gender (P = 0.037), clinical stage (P = 0.038), T classification (P = 0.013) and N classification (P = 0.017). Patients with higher HMGB3 expression had shorter overall survival than those with lower HMGB3 expression. Multivariate Cox analysis indicated that HMGB3 expression is an independent prognostic factor for overall survival (HR = 0.591, 95% CI = 0.379-0.793, P = 0.039). In summary, these findings demonstrate that HMBG3 may be a potential molecular marker for predicting the prognosis of ESCC patients.     

Prognostic value of ISG15 mRNA level in drinkers with esophageal squamous cell cancers

ISG15, the protein encoded by interferon (IFN)-stimulated gene 15, was the first identified ubiquitin-like protein, which could be strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Although the biological activities of ISG15 have yet to be fully elucidated, it is frequently overexpressed in various cancers. As the role of ISG15 in esophageal squamous cell cancer (ESCC) has not been well reported, the current study aimed to elucidate the role of ISG15 in predicting outcomes of ESCC patients. Samples were collected from 153 ESCC patients, including 54 pairs of tumor tissues and non-tumor tissues. Compared with the paired non-tumor tissues, higher expression of ISG15 mRNA were detected in ESCC tissues. The cut-off value 1.28 determined by ROC curve analysis divided the ESCC patients into high and low ISG15 mRNA expression group. High-ISG15 mRNA expression appeared with more frequency in ever-drinkers (P = 0.018). Kaplan-Meier analysis indicated that Low-ISG15 mRNA expression group had a longer cancer-specific survival (CSS) compared with High-ISG15 mRNA expression group. Multivariate analysis revealed that ISG15 mRNA (P = 0.024; hazard ratio, 2.759, 95% CI, 1.841-4.134) as well as Pathological staging (P < 0.001; hazard ratio, 1.634, 95% CI, 1.065-2.505) were independent prognostic factors. Subgroup analysis revealed that the discernibility of ISG15 mRNA level on ESCC outcomes was only pronounced in ever-drinkers (P = 0.026) not in never-drinkers (P = 0.138). ISG15 might serve as a novel prognostic biomarker in drinkers with ESCC.     

Association of nuclear annexin A1 with prognosis of patients with esophageal squamous cell carcinoma

Although recent progress has been made in the diagnosis and treatment of cancer, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. The identification of biomarkers for ESCC prognosis is important for treatment decisions. The aim of this study was to evaluate the relationship between the expressions of Annexin A1 (ANXA1), three prime repair exonuclease 1 (TREX1) and apurinic/apyrimidinic endonuclease-1 (APE1) and clinical outcome of patients with ESCC. The expressions of ANXA1, TREX1 and APE1 in 93 pairs of ESCC and paracancerous tissues were tested using immunohistochemistry. ANX1, TREX1 and APE1 were dysregulated in ESCC. Nuclear expressions of ANXA1 and APE1 were significantly associated with pathologic type (P = 0.004 and 0.040, respectively). Patients with low expression of nuclear ANXA1 had a better prognosis than those with high expression of nuclear ANXA1 (HR = 0. 448, 95% CI 0.236-0.849, P = 0.014), especially for those with histologic grade 1 and 2 (HR = 0.303, 95% CI: 0.155-0.593, P < 0.001). In conclusion, nuclear ANXA1 may be potentially used as a prognostic biomarker for ESCC.     

Overexpression of pituitary tumor transforming gene (PTTG) is associated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma

Pituitary tumor transforming gene (PTTG) is a newly identified proto-oncogene that has been shown to be aberrantly overexpressed in a subset of human cancers. The aim of the present study was to examine PTTG expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance. PTTG protein expression was analyzed in 108 archived, paraffin-embedded primary ESCC specimens by immunohistochemistry and correlated with clinicopathological parameters and patients’ outcome. Overexpression of PTTG was observed in 38.0% (41/108) of primary ESCC tissues and significantly correlated with differentiation, TNM stage, lymph node metastasis, and depth of invasion (P < 0.05). Kaplan–Meier curves showed that ESCC patients with tumors expressing high levels of PTTG had substantially shorter overall survival compared with patients expressing low levels of PTTG (P = 0.022, log-rank test). Cox multivariate regression analysis revealed that overexpression of PTTG was an independent prognostic factor in overall survival for ESCC patients (hazard ratio was 2.35, P = 0.009). Overall, our data suggest that overexpression of PTTG may contribute to the malignant progression of ESCC and serve as a novel prognostic indicator for patients with ESCC.     

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma

Background: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). Patients and methods: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients’ outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. Results: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn’t improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). Conclusions: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.     

TRIP13 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma

Thyroid receptor-interacting protein 13 (TRIP13), a member of the AAA + ATPase super-family, has been proved to be upregulated and identified as a prognostic factor in multiple human cancers, However, the role of TRIP13 in esophageal squamous cell carcinoma (ESCC) and its clinic relevance remains unclear. In the present study, we performed database-mining and detected TRIP13 expression in 158 tissue samples (79 ESCC tissue and 79 matched adjunct non-cancerous tissues). We further investigated the correlation between TRIP13 expression and clinicopathological features and overall survival. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of TRIP13 in ESCC patients. In addition, the mechanisms involved in TRIP13 tumor-promoting effect was investigated. Data showed that TRIP13 expression was significantly increased in ESCC tissues, compared with the matched adjunct non-cancerous tissues. Expression of TRIP13 is significantly correlated with T status (P = 0.027), lymphatic metastasis (P = 0.017), and clinical stages of ESCC (P = 0.009). Kaplan-Meier analyses showed that patients with high TRIP13 expression had poor overall survival (P = 0.0022). Multivariate analysis indicated that TRIP13 expression might be an independent prognostic factor in ESCC patients (HR, 1.778, 95% confidence interval = 0.959–3.296, P = 0.028). Furthermore, downregulating TRIP13 in EC109 cell significantly attenuated the cell proliferation and progression, possibly by β-catenin regulated EMT pathway.Conclusions: Our study demonstrated that TRIP13 might be a tumor promoting factor in ESCC and a promising prognostic indicator for ESCC patient.     

Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis

BackgroundThe gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.MethodWe searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.ResultsSixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43–1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19–3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17–3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08–6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23–2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).ConclusionsHigh CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.     

Prognostic value of osteopontin expression in esophageal squamous cell carcinoma: A meta-analysis

ObjectiveTo explore the prognostic role of osteopontin (OPN) overexpression in esophageal squamous cell carcinoma (ESCC).MethodsThe PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Data (CBM) and VIP databases were searched from the establishment dates of the databases to March 31, 2019, for potentially related studies. Stata 12.0 software was used for statistical analyses, and the hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the correlation of OPN overexpression with the overall survival (OS) and progression-free survival (PFS) of ESCC patients.ResultsA total of 8 studies involving 811 patients from China or Japan were included. OPN overexpression was demonstrated to be significantly associated with poor OS (HR = 1.86, 95% CI: 1.22–2.83, P = 0.004), with high heterogeneity (I² = 61.2%, P = 0.012), and poor PFS (HR=1.63, 95% CI: 1.08–2.47, P = 0.020), without heterogeneity (I² = 0.0%, P = 0.839). Subgroup analysis results were similar to the pooled results.ConclusionOPN overexpression might serve as a promising independent prognostic risk factor in Chinese and Japanese ESCC patients. However, more well-designed studies enrolling more patients are still needed to verify our findings.     

Significance of elevated ERK expression and its positive correlation with EGFR in Kazakh patients with esophageal squamous cell carcinoma

Extracellular signal-regulated kinases (ERKs) are activated by the MAPK pathway. ERKs are downstream effectors of the epidermal growth factor receptor (EGFR), which belongs to the receptor tyrosine kinases family. Studies on the activation of the EGFR-ERK pathway in Kazakh patients with esophageal squamous cell carcinoma (ESCC) have not been reported. Using immunohistochemical staining on tissue microarrays, we investigated the protein expression of EGFR and ERK in 90 ethnic Kazakh patients with ESCC and 48 adjacent normal esophageal tissues (NETs). EGFR and ERK1 expression was localized in the cytoplasm, whereas ERK2 expression was localized in the nucleus. Both were more highly expression in the ESCC tissues than in the NETs, and the difference was considered significant (P = 0.003, 0.002, and 0.005, respectively). ERK1 and EGFR expression was positively correlated with lymph nodes metastasis (P = 0.011 and 0.013, respectively). ERK1 staining was also significantly associated with tumor-node-metastases stage of ESCC (P = 0.044). ERK2 staining was significantly associated with Histological grade (P = 0.012). Furthermore, ERK1 and EGFR expression in the ESCC tissues were positively correlated (r = 0.413, P < 0.001); EGFR was more highly expressed in the ESCC tissues with high ERK1 expression than in the ESCC tissues with low ERK1 expression (4.95 ± 0.57 vs. 3.21 ± 0.35, P = 0.01). This study is thus far the first to demonstrate the correlation between EGFR overexpression and ERK overexpression in Kazakh patients with ESCC. This correlation suggests that the EGFR-ERK signaling pathway participates in ESCC progression and can thus be used as a prognostic marker.     

Overexpression of matriptase correlates with poor prognosis in esophageal squamous cell carcinoma

Matriptase is one of the type II transmembrane serine proteases and is known to be involved in cancer progression. Increased matriptase expression has been reported in a variety of human cancers, and its association with poor prognosis has been highlighted in some cancer types. However, its exact role in cancer progression and its effect on patient survival in esophageal squamous cell carcinoma (ESCC) are still unclear. We performed immunohistochemical staining of matriptase in 171 ESCC samples after antibody validation and evaluated the association of its expression with clinicopathological parameters and prognosis. High matriptase expression was observed in 38.6 % (66/171) of ESCC samples and more frequently in N3 stage and in poorly differentiated tumors. Both overall survival (OS) and disease-free survival (DFS) were significantly lower for patients with high expression of matriptase than for patients with low expression (5-year OS rate, 38.6 vs 55.3 %; p?=?0.034 and 5-year DFS rate, 30.5 vs 49.4 %; p?=?0.007). High matriptase expression was an independent prognostic factor for OS [hazard ratio (HR), 1.65 (95 % confidence interval (CI), 1.01–2.68); p?=?0.045] and for DFS [HR, 1.79 (95 % CI, 1.14–2.81); p?=?0.012]. In conclusion, higher expression of matriptase is an independent prognostic factor involved in the progression of ESCC, which suggests that matriptase is a factor in ESCC tumor progression and also a potential molecular therapeutic target.     

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.     

Increased HIF-1alpha expression in tumor cells and lymphocytes of tumor microenvironments predicts unfavorable survival in esophageal squamous cell carcinoma patients

The expression of hypoxia-induced factor (HIF)-1α is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1α in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1α expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1α expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1α expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients’ clinicopathological parameters. Patients with high HIF-1α expression in tumor cells or in TILs showed worse survival related to those with low HIF-1α expression. Multivariate analysis demonstrated that expression of HIF-1α in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1α in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1α in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1α in tumor cells and in TILs were positively correlated, and patients with combined high HIF-1α in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1α expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients.     

Elevation in peripheral blood circulating tumor cell number correlates with macroscopic progression in UICC stage IV colorectal cancer patients

Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C, prognostic significance of VEGF-D expression and its association with HIF-1α expression remain elusive in esophageal squamous cell cancer (ESCC). We studied expression of HIF-1α and VEGF-D using immunohistochemistry in 85 resected ESCC specimens and correlated results with patients'' clinicopathologic parameters and survival. Association between expression of HIF-1α and VEGF-D was investigated using a concordance analysis. High expression of HIF-1α and VEGF-D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1α expression correlated well with tumor stage (P = 0.041), whereas VEGF-D expression correlated with tumor stage (P = 0.027) and N status (P = 0.019). Groups of high HIF-1α and VEGF-D showed worse survivals than those of low expression (P = 0.002 and 0.001, respectively). Multivariate analysis supported expression of HIF-1α and VEGF-D as significant survival predictors (P = 0.044 and 0.035, respectively). A concordance rate of 69.5% was observed between expression of HIF-1α and VEGF-D. In conclusion, protein expression of HIF-1α and VEGF-D are independent prognostic predictors. An association between expression of HIF-1α and VEGF-D suggests that these two angiogenic factors are essential in progression of ESCC.     

High level of microtubule-associated protein light chain 3 predicts poor prognosis in resectable esophageal squamous cell carcinoma

Microtubule-associated protein light chain 3 (LC3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC3 by immunohistochemistry in a group of patients with ESCC treated with surgical resection. Tissue microarray that included 253 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of LC3 expression was analyzed statistically. The association of LC3 expression with the ESCC survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. The results showed that the immunostaining of LC3 was distributed in cytoplasm and plasma-membrane. Significantly high LC3 expression was found in ESCC cells compared with that of normal esophageal epithelial cells. Patients with low expression of LC3 demonstrated higher overall survival compared with those with high expression of LC3 (mean of 71.1 months versus 55.5 months, P = 0.022). A similar result was observed for disease-free survival (mean of 68.7 months versus 51.8 months, P = 0.021). In subgroup analysis, LC3 expression could stratify pN0 patients with ESCC. Multivariate analysis showed that the level of LC3 expression was an independent prognostic factor in ESCC (RR = 1.407, P = 0.049). This paper shows high level of LC3 suggests poor prognosis for resectable ESCC patients.     

Down-regulation of miR-503 expression predicate advanced mythological features and poor prognosis in patients with NSCLC

Objective: We aimed to explore what impact miR-503 has on the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Cancer and matched non-malignant lung tissue specimens were collected from 109 patients who underwent surgery in Tanisha Hospital from Jun 2006 to July 2013. Overall survival (OS) curves were analyzed using the Lapland-Meier method, and the differences were examined using log-rank tests. Cox proportional- hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for OS. Results: The relative expression of miR-503 in NSCLC tissues (0.366 ± 0.130) was significantly lower than that in matched noncancerous lung tissues (1.667 ± 1.047, P < 0.01). Statistically significant association was observed between miR-503 expression and lymphatic invasion (P = 0.005), distant metastasis (P = 0.002), TNM stage (P = 0.008), and tumor grade (P = 0.043). Lapland Meier analysis clearly illustrated that the patients with the lower expression of miR-503 had a worse outcome compared to patients with higher miR-503 expression (P = 0.004). Furthermore, multivariate analysis revealed that miR-503 expression level was an independent prognostic factor for overall survival (HR = 3.992, 95% CI: 2.276-9.872; P = 0.018) in NSCLC. Conclusion: In patients with NSCLC, low miR-503 expression is an independent prognostic factor.     

Up-regulation of long non-coding RNA CCAT2 correlates with tumor metastasis and poor prognosis in cervical squamous cell cancer patients

Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention.     

Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors worldwide, with a high malignant degree and poor prognosis. The present study aims to investigate the relationship between pyruvate kinase M2 (PKM2) expression and the prognosis of patients with ESCC. The expression of PKM2 in 86 cases of esophageal carcinoma tissues was tested using immunohistochemistry. The relationship between PKM2 expression and clinical pathological parameters, and their effects on the prognosis of patients with ESCC were analyzed. The expression levels of PKM2 in both cytoplasm and nucleus of ESCC tissues were significantly higher than those in paracancerous tissues (P = 6.73 × 10⁻⁹ and 4.32 × 10⁻⁶, respectively). The Kaplan–Meier analysis showed that nuclear PKM2 expression was closely related to the survival of patients with ESCC (P = 0.005). Patients with high PKM2 expression in the nucleus had significantly shorter survival times than those with low PKM2 expression in the nucleus (hazard ratio for death, 2.358; 95% confidence interval, 1.156–4.812; P = 0.018). No other significant difference was found between PMK2 expression and clinico-pathological features of ESCC patients (all P > 0.05). In conclusion, high PKM2 expression in the nucleus is essential in the pathogenic process of ESCC and may be used to predict the prognosis of patients with ESCC.     

High expression of oncoprotein DEK predicts poor prognosis of small cell lung cancer

Oncoprotein DEK plays an important role in cancer tumorigenesis. To explore the clinical implication of DEK expression on prognostic evaluation in small cell lung cancer (SCLC), 130 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of DEK protein. The correlation between DEK expression and clinicopathological features of SCLC was evaluated using the Chi-square and Fisher’s exact tests, survival rates were calculated using the Kaplan-Meier method and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. IHC analysis demonstrated that DEK protein staining was strongly positive and significantly higher (44.62%) in SCLC compared with either adjacent non-tumor or normal lung tissues (P < 0.001 for both). DEK expression correlated with large tumor size (P = 0.025) and late pathologic stage (P = 0.005). Moreover, it correlated with low disease-free (P = 0.004) and 5-year (P = 0.005) survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with high level DEK expression were significantly lower than those with low level DEK expression (P = 0.006 and P = 0.001, respectively). Furthermore, Cox analysis revealed that DEK expression emerged as a significant independent hazard factor for the overall survival rate of patients with SCLC (HR: 1.594, 95% CI: 1.087-2.336, P = 0.017). In conclusion, DEK plays an important role in the progression of SCLC. DEK may potentially be used as an independent biomarker for the prognostic evaluation of SCLC.