Low expression of PHLPP1 in sacral chordoma and its association with poor prognosis

Sacral chordoma is a rare spine tumor with a high recurrence rate even after optimal therapy. Previous studies have demonstrated that the PI3K/AKT pathway plays a pivotal role in chordoma, and high expression of pAKT is associated with poor prognosis. Recently, PHLPP was recognized to be a tumor suppressor that targets AKT. We analyzed the expression of PHLPP1 and AKT2 in 37 chordoma samples and 11 fetal nucleus pulposus samples by immunohistochemical staining. Of the chordoma cases, 40.5% (15/37) showed strong cytoplasmic staining (score ≥3) for PHLPP1, which was significantly lower than the 90.9% (10/11) of fetal nucleus pulposus samples (P = 0.004). Conversely, strong immunohistochemical staining for AKT2 was observed in 75.7% (28/37) of chordoma samples, which was significantly higher than 36.4% (4/11) of fetal nucleus pulposus (P = 0.021). Kaplan-Meier survival curves and log-rank test showed that patients with high expression of PHLPP1 experienced longer progression free survival time than those with low PHLPP1 expression (P = 0.011). Further multivariate Cox regression analysis indicated that PHLPP1 expression level and surgical approaches were independent risk factors for chordoma recurrence (P = 0.023 and P = 0.022). However, PHLPP1 expression was not statistically related to patients’ total survival time. Conclusively, our results suggest that PHLPP1 plays a crucial role in sacral chordoma, and may be a promising biomarker for prognosis. Meanwhile, manipulation of PHLPP1 expression is also a potential therapeutic approach for the treatment of sacral chordoma.     

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.     

Clinicopathologic and prognostic significance of p21 (Cip1/Waf1) expression in bladder cancer

Recent studies have shown that altered expression p21 is shown to associate with tumorigenesis and tumor progression. To investigate the clinicopathological significance and prognostic value of p21 in bladder cancer (BCa). A total of 48 patients with BCa were included in this study. The correlation between p21 expression and clinicopathologic features and survival was studied. Also, a meta-analysis was performed to investigate the relationship between the p21 and BCa survival. Low p21 expression was detected both in tumor tissues compared with adjacent normal tissues. The expression of p21 was closely associated with advanced pathologic TNM stage (P = 0.001) and tumor grade (P = 0.013). Moreover, patients with low p21 expression had shorter recurrence-free survival (P = 0.016) and overall survival rates (P = 0.039). Multivariate Cox regression analysis revealed that p21 low expression was an independent prognostic factor for recurrence free survival (P = 0.03). Additionally, our meta-analysis. The available outcome data from six articles were examined. A meta-analysis of the HR indicated a significantly poor overall survival (OS, HR: 1.75, 95% CI: 1.38-2.21), recurrence free survival (RFS, HR: 1.83, 95% CI: 1.57-2.15), progression free survival (PFS, HR: 2.02, 95% CI: 1.48-2.75), and cancer specific survival (CSS, HR: 1.89, 95% CI: 1.53-2.33) in patients with low expression levels of p21. Our present results indicated that low p21 expression predicated tumor recurrence and poor prognosis in bladder cancer.     

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.     

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.     

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.     

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.     

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.     

Increased expression of microRNA-150 is associated with poor prognosis in non-small cell lung cancer

Objectives: The aim was to evaluate the clinical significance and prognostic value of tissue miR-150 expression in non-small cell lung cancer (NSCLC) patients. Materials and methods: Quantitative real-time PCR was used to analyze the expression of miR-150. Overall survival (OS) was estimated using the Kaplan-Meier method, and the differences in survival were compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Results: Mean miR-150 levels were significantly higher in NSCLC tissues compared with matched non-cancerous tissues (4.07 ± 2.33 vs. 1.00 ± 0.46, P < 0.0001). The level of miR-150 in NSCLC was strongly correlated with lymph node metastasis (P = 0.04), distant metastasis (P = 0.01) and clinical TNM stage (P = 0.02). Kaplan-Meier analysis showed that the cumulative 5-year OS rate was 40.8% in the high expression group, and 69.2% in the low expression group. The log-rank test showed that the OS rate of patients with high miR-150 expression was significantly poorer than that of the remaining cases (P = 0.007). Conclusion: Our data indicated that overexpression of miR-150 in NSCLC tissues has prognostic value.     

In situ hybridization analysis of the expression of miR-106b in colonic cancer

Background: MicroRNA-106b (miR-106b) is thought to be an oncogenic microRNA that promotes tumor growth and metastasis. The potential predictive value of miR-106b was studied in colonic cancer patients. Methods: The expression of miR-106b was examined in 180 colonic cancer cases using in situ hybridization (ISH) technique and was evaluated semi-quantitatively by examining the staining index. The Correlation of miR-106b expression and clinic-pathological features was analyzed by Spearman Rank Correlation. Wilcoxon signed rank test was used for assessing the expression difference of miRNA-106b between colonic cancerous and para-cancerous ones, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. Results: MiR-106b was higher expressed in para-cancerous tissues, compared with colonic cancerous ones (P < 0.001). A positive correlation of miR-106b levels between colonic and para-cancerous tissues was also observed (CC = 0.523, P < 0.001). Furthermore, the expression of miR-106b was not significantly correlated with clinic-pathological parameters, including gender, age, histological grade, tumor size, pT stage, pN stage, pM stage and pTNM stage of the patients. Histological grade was positively correlated with pT stage (P = 0.011), pN stage (P = 0.036) and pTNM stage (P = 0.009). Patients expressing high levels of miR-106b both in colonic cancer tissues and para-cancerous ones have a relatively longer survival time but the difference is not statistically significant (P = 0.16). Conclusions: The expression difference of miR-106b levels between colonic tissues and para-cancerous tissues is statistically significant, but the miR-106b levels were not quite correlated with clinic-pathological characteristics and overall survival times of patients with colonic cancer. Lower levels of miR-106b may be connected with neoplastic effects due to interference with TGF-β signaling, providing evidence that down-regulation of miR-106b might also play an important role in the progression of the disease. The study results are consistent with the literature and support the notion that miR-106b is an oncogenic microRNA.     

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.     

Increased expression of miRNA-182 in colorectal carcinoma: an independent and tissue-specific prognostic factor

Increasing evidence has revealed that miRNAs play a pivotal role in multiple processes of carcinogenesis, and are being explored as diagnostic, prognostic and predictive biomarker. In this study, we investigated the status of miR-182 expression in colorectal carcinoma (CRC) by in situ hybridization and its underlying clinicopathologic significance for patients with CRC. We found that 79/138 (57.25%) CRCs had high-level expression of miR-182, while 17/67 (25.37%) normal mucosa tissues had high-level expression of miR-182. The expression level of miR-182 was remarkably up-regulated in CRC tissues compared with non-neoplastic normal tissues (P < 0.001). The over-expression of miR-182 in cancer parenchyma cells in CRC were strongly correlated with T-stage (P = 0.020), lymph node metastasis (P = 0.003), distant metastasis (P = 0.002), and Dukes’ stage (P = 0.005) in patients with CRC. Patients with high-level expression of miR-182 had short overall survival time than those with low-level expression of miR-182 (P < 0.001). Univariate and multivariate survival analyses further showed that miR-182 expression was a potential unfavorable prognostic factor for CRC, suggesting a potential application of miR-182 in prognosis prediction and therapeutic application in CRC.     

Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded tissues of breast cancer

Background: MiR-24/378 is thought to be onco-miRNAs for their ability of enhancing tumor growth. The objective of this study was to evaluate the potential predictive value of miR-24/378 expression in formalin-fixed paraffin-embedded tissues of breast cancer patients. Methods: The expression of miR-24/378 was examined in 101 breast cancer patients and 40 controls using real-time quantitative PCR. All statistical analyses were performed using SPSS16.0. Results: We found that miR-24 and miR-378 were significantly up-regulated in breast cancer patients compared with controls (all P < 0.01). The expression levels of the two miRNAs were highly correlated with each other in breast cancer patients, with r = 0.778 between miR-24 and miR-378. Moreover, the two miRNAs exhibited great capability of discriminating between cancer patients and controls by ROC analysis. MiR-24 and miR-378 showed 0.79 and 0.807 AUC values respectively. Conclusions: Over-expression of miR-24 and miR-378 in FFPE tissue of breast cancer patients might conduct as an ideal source for biomarker discovery and validation in breast cancer patients.     

miR-21表达异常与乳腺癌临床病理特征及预后的关系

目的： 应用荧光定量PCR技术研究miR-21表达量与乳腺癌临床病理特征及患者预后的关系。方法: 搜集具有5年以上随访资料的乳腺癌病例113例,从甲醛固定、石蜡包埋（FFPE）乳腺癌(BRCA)及其癌旁组织(NATs)中提取总RNA,应用荧光定量RT-PCR技术检测miR-21在乳腺癌及其癌旁组织中的表达量。结果: 与相应癌旁组织比较,miR-21在乳腺癌组织中表达显著上调（P<0.01）,平均上调倍数为1.74 ± 0.48。miR-21表达上调水平与乳腺癌临床分期(P<0.01)、淋巴结转移（P<0.01)及预后［hazard ratio (HR)=5.476, P<0.01］相关。 Cox多重回归分析显示miR-21相对表达量(HR=4.133, P<0.01)为乳腺癌的独立预后因素之一。结论: miR-21表达上调与乳腺癌患者预后不良有关,其可能是一种潜在的乳腺癌独立预后指标。     

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC.Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established.Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively.Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.     

Upregulation of microRNA-23a/b promotes tumor progression and confers poor prognosis in patients with gastric cancer

Background and purpose: To investigate the clinical significance of microRNA (miR)-23a and miR-23b expression in human gastric cancer (GC). Methods: Quantitative RT-PCR was performed to detect the expression changes of miR-23a and miR-23b in 160 human GC tissues and paired normal mucosa. The associations between miR-23a and miR-23b expression, and the selected clinicopathological characteristics and patients’ prognosis were also evaluated. Results: MiR-23a (GC vs. Normal: 3.98 ± 1.23 vs. 2.29 ± 1.12, P < 0.001) and miR-23b (GC vs. Normal: 3.70 ± 1.24 vs. 1.58 ± 1.18, P < 0.001) expression were both increased dramatically when compared with paired normal mucosa. Notably, the expression levels of miR-23a in GC tissues were positively correlated with those of miR-23b (Spearman correlation coefficient r = 0.77, P < 0.001). Then, the coexpression of miR-23a and miR-23b (miR-23a-high/miR-23b-high) in GC tissues was significantly associated with the advanced TNM stage (P < 0.001), the presence of lymph node metastasis (P = 0.008) and the great depth of invasion (P = 0.02). Furthermore, both univariate and multivariate analyses showed that miR-23a/miR-23b co-expression was an independent predictor for unfavorable overall survival. Conclusions: These results suggest that the dysregulation of miR-23a and miR-23b may be implicated in the progression of human GC. Combined expression of miR-23a and miR-23b appears to be a valuable marker for prognosis of this disease.