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 microRNA-196a predicts poor prognosis in human ovarian carcinoma

Objective: Overexpression of MicroRNA-196a (miR-196a) has recently been reported in different types of human cancers. However, the prognostic value of miR-196a in ovarian carcinoma remains unknown. In this study, we investigated the expression of miR-196a in ovarian carcinoma and its relationship with tumor progression and clinical prognosis. Methods: The expression level of miR-196a was examined by quantitative Real-time PCR (qRT-PCR) in surgically removed ovarian cancer tissues and ovarian cancer cell lines. The correlation between miR-196a expression and clinical features and prognosis were statistically analyzed. Results: The results showed that the miR-196a expression was significantly upregulated in tumor tissues and ovarian cancer cell lines compared with that in normal ovarian surface tissues and normal ovarian epithelial cells. Moreover, miR-196a expression was positively correlated with FIGO stage (P <0.001), tumor size (P =0.020), and lymph nodes metastasis (P =0.019). Kaplan-Meier analysis demonstrated that high levels of miR-196a expression was associated with poorer overall survival (P <0.001) and recurrent-free survival (P =0.003), especially in patients with advanced disease (P =0.002). Multivariate analysis suggested that miR-196a expression was an independent prognostic factor for overall survival of patients with ovarian carcinoma. Conclusions: In conclusion, miR-196a may play an important role in the progression of ovarian carcinoma, and could be used as an independent prognostic biomarker for patients with ovarian carcinoma.     

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival

Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.     

Up-regulation of miR-630 in clear cell renal cell carcinoma is associated with lower overall survival

Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-630 has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer and gastric cancer. However, the regulation of miR-630 in clear cell renal cell carcinoma (ccRCC) has not yet been reported before. Methods: Expression of miR-630 was evaluated by quantitative real-time PCR in tumour and their normal matched tissues in n = 92 ccRCC patients, and its association with overall survival of patients was analyzed by statistical analysis. Results: The expression level of miR-630 was significantly higher in renal cancer in comparison to normal matched tissue (P < 0.05). It is also proved that miR-630 expression was to be associated with renal cancer histologic grade, lymphnode metastasis, distant metastasis (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that high miR-630 expression was associated with poor prognosis in ccRCC patients. miR-630 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis. Conclusions: The study proves for the first time that miR-630 is upregulated in a majority of ccRCC patients. It also shows that miR-630 expression is an independent prognostic factor for patients with renal cancer, which might be a potential valuable biomarker for ccRCC.     

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.     

microRNA-195-Cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma

Background and purpose: Previous studies observed the downregulation of microRNA (miR)-195 in esophageal squamous cell carcinoma (ESCC) tissues, confirmed cell division cycle 42 (Cdc42) as one target gene of miR-195, and demonstrated that miR-195 may act as a tumor suppressor in ESCC by regulating Cdc42 expression. This study aimed to explore the association of miR-195 and Cdc42 combined expression with clinicopathologic factors and prognosis. Methods: Expression of miR-195 and Cdc42 mRNA in 98 pairs of ESCC and paracancerous tissues were detected using real-time quantitative RT-PCR. Results: miR-195 downregulation and Cdc42 upregulation were both prevalent in ESCC tissues, and negatively correlated with each other. In addition, miR-195 expression negatively correlated with TNM stage (P=0.008) and lymphatic metastasis (P=0.022), while Cdc42 expression positively correlated with TNM stage (P=0.011) and tumor differentiation (P=0.024). Moreover, combined expression of miR-195 and Cdc42 (miR-195/Cdc42) was found to be prognostic indicators for progression-free survival and overall survival of ESCC patients both in univariate and multivariate analyses. Conclusion: The main findings of this study indicate the involvement of miR-195-Cdc42 axis in the progression of ESCC and suggest that the combined aberrant expression of miR-195 and Cdc42 mRNA can serve as a promising unfavorable prognostic biomarker in ESCC.     

Aberrant expression of microRNA-26b and its prognostic potential in human cervical cancer

Background: microRNA-26b (miR-26b) is reported to be downregulated in many human malignancies and function as a tumor suppressor. However, the roles of miR-26b expression in cervical cancer progression are unclear. The aim of this study was to investigate the clinicopathological or prognostic significance of miR-26b in human cervical cancer. Methods: A cohort of 88 paired of cervical cancer and the adjacent normal cervical epithelial tissues were collected. Quantitative RT-PCR (qRT-PCR) assay was used to detect the expression of miR-26b and its correlations with clinicopathological factors were statistically analyzed. Finally, the survival was assessed by the Kaplan-Meier method and proportional hazards model. Results: The expression level of miR-26b in cervical cancer tissues was significantly lower than that in the adjacent normal cervical tissues (P<0.001). Reduced miR-26b was observed to be significantly correlated with advanced FIGO stage, higher incidence of lymph node metastasis and recurrence of cervical cancer patients (P=0.002, 0.036 and 0.029, respectively). In addition, patients with low-miR-26b expression showed poorer recurrence-free survival (RFS) and overall survival (OS) than those with high-miR-26b expression (P=0.0043 and 0.0015, respectively). Furthermore, multivariate analyses demonstrated that low miR-26b expression was an independent prognostic factor for predicting the 5-year RFS and OS of cervical cancer patients (P=0.013 and 0.007, respectively). Conclusion: Our results showed that reduced miR-26b was correlated with tumor development and poor prognosis in human cervical cancer. The status of miR-26b expression may be a potential prognostic biomarker for cervical cancer patients.     

Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer

Introduction: MicroRNA-124 (miR-124) has been proven dysregulated in several human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to investigate the clinical significance of miR-124 expression in NSCLC. Methods: Expression levels of miR-124 in 92 pairs of NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: miR-124 expression level was significantly lower in NSCLC tissues compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124 expression group was significantly shorter than that of high miR-124 expression group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was also significantly shorter than that of high miR-124 expression group (P < 0.05). In a multivariate Cox model, we found that miR-124 expression was an independent prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05). Conclusions: Our results offer the convincing evidence that miR-124 may play key roles in the progression of lung cancer and that the down-regulated expression of miR-124 may be independently associated with shorter OS and DFS of patients, suggesting that miR-124 might be a potential marker for further risk stratification in the treatment of lung cancer.     

MicroRNA-153 expression and prognosis in non-small cell lung cancer

Background: miR-153 has been found to be significantly decreased in non-small cell lung cancer (NSCLC) tissues; however, its clinical significance has not been investigated. Methods: The expression patterns of miR-153 in 137 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed using qRT-PCR. The relationships between miR-153 expression and clinicopathological parameters were examined by chi-square test. Kaplan-Meier method and the log-rank test were used to determine the difference in overall survival (OS) rates between two groups. Results: The expression of miR-153 was reduced significantly, compared with adjacent normal lung tissues (P<0.05). We observed that the expression level of miR-153 was positively correlated with the clinical stage (P=0.005), lymph node status (P=0.014), distant metastasis (P=0.004), and differentiated degree (P<0.001) in NSCLC patients. According to the Kaplan-Meier survival analysis, the patients with low miR-153 expression exhibited evidently poorer overall survival rates than those with high miR-153 expression (P=0.003). Multivariate analysis showed that the expression of miR-153 was an independent and significant factor associated with poor OS rates (P=0.002). Conclusion: Decreased expression of miR-153 might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.     

High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma

Biglycan (BGN), an extracellular matrix component, has been reported to play a crucial role in the tumor progression of various cancers. However, the relation between the expression of BGN and clinical prognosis has not been studied yet. We therefore carry out the present study to elucidate the role of BGN in predicting outcomes of patients with esophageal squamous cell carcinoma (ESCC). In this study, the expression of BGN in 170 cases of ESCC tissues and matched 46 adjacent non-tumorous tissues was measured by quantitative real-time PCR and immunohistochemistry. Upregulation of BGN occurred in approximately 60% of primary ESCCs compared with their non-tumor counterparts. In addition, high expression of BGN was significantly associated with clinical stage (P = 0.009), tumor invasion (P = 0.006) and lymph node metastasis (P = 0.046). The 5-year disease-specific survival (DSS) in high expression of BGN group is poorer than that in low level expression group (36.8% VS 57.4%, P = 0.006). Stratified analysis according to the pathological stage revealed its discernibility on DSS was only pronounced in patients with advanced clinical stage (P = 0.010). Cox multivariate analysis revealed that pathologic N category (P < 0.001; hazard ratio, 2.482, 95% CI, 1.576-3.909) and BGN expression (P = 0.019; hazard ratio, 1.713, 95% CI, 1.092-2.688) were two independent prognostic factors. The findings of the present study provide evidence that BGN represents a potential novel prognostic biomarker for resected ESCC patients in advanced clinical stage.     

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.     

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.     

miR-145 expression level in tissue predicts prognosis of patients with esophageal squamous cell carcinoma

BackgroundMicroRNA-145 (miR-145) is commonly down-regulated and has been identified as a tumor-suppressive miRNA in multiple types of cancers, as well as in esophageal squamous cell carcinoma (ESCC). In the present study, the clinical significance and prognostic value were investigated in ESCC.MethodsA total of 126 patients with ESCC who underwent surgery were included in the present study. miR-145 expression was determined using quantitative real-time polymerase chain reaction assay (qRT-PCR) and was further correlated with patients’ clinicopathological parameters. Overall survival was estimated by using Kaplan-Meier method, and univariate analysis was conducted by log-rank test. The Cox proportional hazards model was used in the multivariate analysis.ResultsmiR-145 expression levels in ESCC tissues were significantly decreased compared with the adjacent normal zones (P < 0.001). We observed that the expression level of miR-145 was positively correlated with the tumor differentiation (P = 0.015), lymph node status (P = 0.007), distant metastasis (P = 0.008), and TNM stage (P = 0.033). ESCC patients with low miR-145 expression level had shorter overall survival than those with high miR-145 expression level (log-rank test, P = 0.032). Furthermore, multivariate Cox regression analysis showed that miR-145 expression level was independent factor in predicting the overall survival of ESCC patients (HR = 1.993, 95% CI: 1.277–8.283, P = 0.023).ConclusionsOur findings indicated that miR-145 expression may be a useful prognostic marker that could be used for predicting overall survival of patients with ESCC.     

Down-regulation of microRNA-126 and microRNA-133b acts as novel predictor biomarkers in progression and metastasis of non small cell lung cancer

Objective: MiRNAs play crucial roles in progression of cancer. However, the underlying mechanisms of miRNAs in non small cell lung cancer are still poorly understood. The aim of this study was to investigate the expression level of microRNA-126 (miR-126) and microRNA-133b (miR-133b) and also their association with clinicopathological features in patients with non small cell lung cancer (NSCLC). Methods: Total RNA was purified from NSCLC tissues and adjacent non-tumor tissues and then quantitative real-time PCR (qRT-PCR) was used to evaluate the expression rate of microRNAs. Furthermore, the association of miR-126 and miR-133b level with clinicopathological features and prognosis were evaluated. Results: Our findings showed that expression of miR-126 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. On the other hand, a lower expression of miR-133b was seen in NSCLC tissues when compared with adjacent non-tumor tissues. In term of miR-126, our results showed that miR-126 was associated with tumor stage and lymph nodes metastasis (P<0.05). In term of miR-133b, our finding indicated that decreased expression of miR-133b was correlated with advanced tumor stage and lymph nodes metastasis (P<0.05). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-126 and miR-133b had a shorter overall survival (log-rank test; P<0.05). Multivariate Cox proportional hazards model revealed that low expression of miR-126 and miR-133b, advanced tumor stage and lymph nodes metastasis were independent prognostic factors for overall survival of NSCLC patients. Conclusions: These findings suggested that miR-126 and miR-133b might play a key role in the progression and metastasis of NSCLC and would be applied as a novel therapeutic agent.     

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.     

Decreased expression of microRNA-20a promotes tumor progression and predicts poor prognosis of cutaneous squamous cell carcinoma

Background: MicroRNA-20a (miRNA-20a or miR-20a) plays a key role in tumorigenesis and progression. But the prognostic value of miR-20a in cutaneous squamous cell carcinoma (CSCC) remains unclear. The aim of this study was to identify the association of miR-20a and the prognosis of CSCC patients. Methods: The miR-20a expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR) in 152 CSCC tissues and matched adjacent normal tissues. Kaplan-Meier and Cox regression analysis were utilized to determine the association of miR-20a with overall survival as well as the prognosis of CSCC patients. Results: The expression of miR-20a was lower in CSCC tissues compared with adjacent normal tissues (P=0.000). Moreover, the expression of miR-20a was closely correlated with TNM stage (P=0.013). Kaplan-Meier analysis showed that patients with low miR-20a expression had significantly poorer overall survival than those with high miR-20a expression (P<0.05). Multivariate analysis revealed that miR-20a expression (P=0.001, HR=3.262, 95% CI: 1.635-6.520) could influence the prognosis and might be an independent prognostic predictor in CSCC. Conclusions: Our results indicated that low miR-20a expression was associated with tumor stage of CSCC and suggested that miR-20a expression would be a novel biomarker for predicting clinical outcomes in CSCC patients. The inhibition of miR-20a might even become a new therapeutic method for the treatment of CSCC.     

MicroRNA-148b is down-regulated in non-small cell lung cancer and associated with poor survival

Background: The aim of this study was to clarify the clinicopathological significance of miRNA-148b (miR-148b) expression in NSCLC, and to explore the correlation between miR-148b level and the prognosis of patients with NSCLC. Methods: 151 patients diagnosed with NSCLC between May 2007 and April 2012 were included in the present study. Real-time RT-PCR method was used to assess the expression levels of miR-148b. The differences between two groups were assessed using Student’s t -test, and the Kaplan-Meier method was used to estimate overall survival. Results: The expression of miR-148b was decreased in tumor tissues compared to corresponding adjacent normal lung tissues (0.37 ± 0.12 vs. 1.00 ± 0.53, P < 0.05). Low miR-148b expression was significantly associated with TNM stage (P = 0.014), lymph node metastasis (P = 0.031), and distant metastasis (P = 0.008). Kaplan-Meier survival analysis showed that patients with low expression of miR-148b had significantly worse overall survival rates compared with those who had cancers with high miR-148b expression (log-rank test P = 0.039). Furthermore, multivariate Cox proportional hazards model analysis showed that miR-148b expression was independently associated with overall survival of patients with NSCLC (HR = 2.357, 95% CI: 1.612-9.212, P = 0.011). Conclusion: our data indicate that decreased expression of miR-148b in NSCLC tissues has prognostic value.