Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan–Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525?±?1.233 vs. 1.512?±?0.784, P?<?0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P?=?0.026), histological differentiation (P?=?0.039), tumor stage (P?=?0.006), and the presence of metastasis (P?<?0.001). Moreover, Kaplan–Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P?<?0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.     

Aberrant TIG1 methylation associated with its decreased expression and clinicopathological significance in hepatocellular carcinoma

Recently, it has been reported that tazarotene-induced gene 1 (TIG1) methylation was frequently detected in a variety of human cancers. However, the relationship between the TIG1 methylation and the characteristics of hepatocellular carcinoma (HCC) remains unknown. The aim of present study was to observe the promoter methylation of TIG1 in HCC tissues and assess its prognostic significance for HCC. Real-time quantitative polymerase chain reaction and methylation-specific polymerase chain reaction were used, respectively, to examine the mRNA expression and methylation status of TIG1 in 91 pairs of HCC and adjacent noncancerous tissues. The mRNA expression level of TIG1 was significantly lower in HCC tissues than in adjacent noncancerous tissues. The rate of TIG1 promoter methylation was significantly higher in HCC tissues than in adjacent noncancerous tissues (P?<?0.001). A strong correlation between downregulation and promoter methylation was found in these tumors (P?<?0.001). More importantly, TIG1 methylation status was related to tumor size (P?=?0.015), histological differentiation (P?=?0.004), and tumor stage (P?<?0.001). Kaplan–Meier survival analysis showed that TIG1 promoter hypermethylation was associated with a worse outcome in patients with HCC. Further, Cox multivariate analysis indicated that TIG1 methylation status was an independent prognostic factor for the overall survival rate of HCC patients. In conclusion, our data suggested that epigenetic silencing of TIG1 gene expression by promoter hypermethylation may play an important role in HCC.     

Expression of NEDD9 in pancreatic ductal adenocarcinoma and its clinical significance

The aim of this study was to investigate the expression and prognostic significance of NEDD9 in pancreatic ductal adenocarcinoma (PDA). Expressional levels of NEDD9 mRNA and protein in paired pancreatic cancer lesions and adjacent noncancerous tissues were examined by quantitative real-time PCR and western blotting. NEDD9 expression was analyzed by immunohistochemistry in 106 patients with PDA. The correlations between NEDD9 immunostaining levels and clinicopathologic factors, as well as the follow-up data of patients, were analyzed statistically. NEDD9 protein and mRNA levels were elevated in pancreatic carcinoma lesions compared with the paired adjacent noncancerous tissues. A high level of expression of NEDD9 was significantly correlated with clinical staging (P?<?0.001), lymph node metastasis (P?<?0.001), and histological differentiation (P?<?0.001). Patients with a higher NEDD9 expression had a significantly shorter survival time than those patients with lower NEDD9 expression. The multivariate analysis revealed that NEDD9 could serve as an independent factor of poor prognosis. Our finding indicates that NEDD9 could be used as prognostic molecular marker and therapeutic target for PDA.     

Prognostic value of centromere protein-A expression in patients with epithelial ovarian cancer

Altered expression of centromere protein-A (CENP-A) is observed in various types of human cancers. However, the clinical significance and pathological role of CENP-A in epithelial ovarian cancer (EOC) remains unclear. The main objective of this investigation was to clarify the relationships between CENP-A expression and the clinicopathological features of patients with EOC. Real-time quantitative PCR and Western blot were performed to examine CENP-A expression in 20 pairs of fresh-frozen EOC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the CENP-A expression levels on 120 archival EOC paraffin-embedded samples. Prognostic outcomes correlated with CENP-A were examined using Kaplan–Meier analysis and Cox proportional hazards model. Our results showed that the expression levels of CENP-A mRNA and protein in EOC tissues were both significantly higher than those in noncancerous tissues. By immunohistochemistry, the data revealed that high CENP-A expression was significantly correlated with pathological grade (P?=?0.02) and International Federation of Gynecology and Obstetrics stage (P?=?0.006). Consistent with these results, we found that high expression of CENP-A was significantly correlated with poor survival in EOC patients (P?<?0.001). Furthermore, Cox regression analyses showed that CENP-A expression was an independent predictor of overall survival. Our data suggest that CENP-A could play an important role in EOC and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of EOC.     

Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer

Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P?=?0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P?=?0.005 and P?=?0.045, respectively). Kaplan–Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P?<?0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.     

Increased FAT10 expression is related to poor prognosis in pancreatic ductal adenocarcinoma

It has been reported that FAT10 plays an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. However, the clinical and functional significance of FAT10 expression has not been characterized previously in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to assess FAT10 expression and to explore its contribution to PDAC. Real-time quantitative PCR was performed to examine FAT10 expression in 38 pairs of fresh frozen PDAC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the FAT10 expression levels on 134 archival PDAC paraffin-embedded samples. The relationship between FAT10 mRNA expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between FAT10 expression and prognosis of PDAC patients. The relative mRNA expression of FAT10 was significantly higher in PDAC tissues than in adjacent noncancerous tissues (P?<?0.001). By immunohistochemistry, the data revealed that high FAT10 expression was significantly correlated with clinical stage (P?<?0.001), histological differentiation (P?=?0.004), and lymph node metastasis (P?=?0.013). Consistent with these results, we found that high expression of FAT10 was significantly correlated with poor survival in PDAC patients (P?<?0.001). Furthermore, Cox regression analyses showed that FAT10 expression was an independent predictor of overall survival. In conclusion, this study confirmed the overexpression of FAT10 and its association with tumor progression in PDAC. It also provided the first evidence that FAT10 expression in PDAC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of PDAC.     

Expression of CHD1L in bladder cancer and its influence on prognosis and survival

Chromodomain helicase/ATPase DNA-binding protein 1-like (CHD1L) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of CHD1L in bladder cancer (BC) has not been thoroughly elucidated. The aim of this study is to investigate the relationship of CHD1L expression with clinicopathological parameters and prognosis in BC. Immunohistochemistry was carried out to investigate the protein expression of CHD1L in 153 BC tissues and 87 adjacent noncancerous tissues. Our data found that CHD1L protein expression was significantly higher in BC tissues than in adjacent noncancerous tissues (P?<?0.001). CHD1L overexpression was significantly correlated with histologic grade (P?=?0.005) and tumor stage (P?=?0.009). The Kaplan–Meier survival analysis revealed that survival time of patients with high CHD1L expression was significantly shorter than that with low CHD1L expression. Multivariate analysis further demonstrated that CHD1L was an independent prognostic factor for patients with BC. In conclusion, CHD1L is likely to be a valuable marker for carcinogenesis and progression of BC. It might be used as an important diagnostic and prognostic marker for BC patients.     

Expression and clinical significance of STIP1 in papillary thyroid carcinoma

The aim of this study was to detect stress-induced phosphoprotein 1 (STIP1) expression in papillary thyroid carcinoma (PTC) and to analyze its association with prognosis of PTC patients. Immunohistochemistry was performed to detect the expression of STIP1 in 113 PTC tissues and paired adjacent noncancerous tissues. The χ2 test was used to analyze the relationship between STIP1 expression and clinicopathological characteristics. Survival curves were plotted by the Kaplan–Meier method and compared using the log-rank test. Survival data was evaluated using univariate and multivariate Cox regression analysis. We identified abnormally elevated expression of STIP1 protein in PTC tissues compared to paired adjacent noncancerous tissues. Clinicopathological analysis showed that STIP1 expression was significantly correlated with tumor size (P?=?0.017), lymph node metastasis (P?=?0.007), and TNM stage (P?=?0.026). Patients with higher STIP1 expression had shorter overall survival time, whereas those with lower STIP1 expression had longer survival time. Multivariate analysis suggested that STIP1 expression might be an independent prognostic indicator (P?<?0.05) for the survival of patients with PTC. In conclusion, our findings provide evidences that positive expression of STIP1 in PTC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with PTC.     

Prognostic significance of BMP7 as an oncogene in hepatocellular carcinoma

This study aims to evaluate the association between BMP7 tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The expression of BMP7 mRNA in HCC was characterized using real-time PCR and 30 pairs of fresh frozen HCC tissues and corresponding noncancerous tissues. BMP7 protein expression in HCC was confirmed using immunohistochemistry on a tissue microarray chip. Finally, BMP7 expression was correlated with conventional clinicopathological features of HCC and patient outcome. The expression of BMP7 mRNA and protein in HCC cells was much higher than in normal hepatic cells. Our results showed that the high expression of BMP7 in HCC was related to tumor size (p?<?0.001), histological differentiation (p?=?0.041), serum AFP (p?=?0.007), and tumor stage (p?<?0.001). Kaplan–Meier survival analysis showed that a high-expression level of BMP7 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that BMP7 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high-expression level of BMP7 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that BMP7 may be a potential target of antiangiogenic therapy for HCC.     

RETRACTED ARTICLE: Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression,metastasis, and unfavorable prognosis of human osteosarcoma

Despite the progress in therapeutic targets, it remains dissatisfactory for most osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it is required to determine the involved mechanisms of osteosarcoma. The aim of this study was to investigate the expression level of MiR-217 and miR-646 and also their association with clinicopathological features in patients with osteosarcoma. Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues, and then quantitative real-time PCR was applied to evaluate the expression level of microRNAs. Our result suggested that miR-217 expression was remarkably deceased in osteosarcoma bone tissue when compared with noncancerous bone tissues (mean?±?SD 5.32?±?1.231, 2.01?±?0.78; P?=?0.024) and miR-646 expression decreased in osteosarcoma bone tissue in comparison with normal tissues (mean?±?SD 4.56?±?1.45, 1.76?±?1.24; P?=?0.041). Our findings indicated that decreased expression of MiR-217 and miR-646 was strongly correlated with high tumor, node, and metastasis (TNM) stage (P?=?0.015, P?=?0.002) and large cancer diameter (P?=?0.041, P?=?0.053). Kaplan-Meier survival and log-rank analysis indicated that shorter overall survival was strongly linked to decreased expression of miR-217 and miR-646 (log-rank test P?=?0.034, P?=?0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis has showed that reduction of miR-217 expression (P?=?0.001), TNM stage (P?=?0.046), and lymph node metastasis (P?=?0.006) were independently linked to a short-time survival of patients. In terms of miR-646, low expression of miR-646 (P?=?0.021), TNM stage (P?=?0.052), and tumor size (P?=?0.043) were independently associated with poor survival of patients as prognostic factors. Our findings suggested that downregulation of MiR-217 and miR-646 was associated with progression of osteosarcoma. MiR-217 and miR-646 may play a key role in suppression of tumor in osteosarcoma and would be applied as a novel therapeutic agent.