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.     

Neuropilin-1 is overexpressed in osteosarcoma and contributes to tumor progression and poor prognosis

Aim

Neuropilin (NRP)-1, a co-receptor for vascular endothelial growth factor (VEGF), plays an important role in angiogenesis and malignant progression of many cancers. However, the involvement of NRP-1 in osteosarcoma is not completely understood. The aim of this study was to investigate the expression pattern and clinical significance of NRP-1 in human osteosarcoma.

Methods

NRP-1 mRNA and protein expression levels were detected by RT-PCR and Western blot assays, respectively, using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the association of NRP-1 expression with clinicopathological factors or survival of osteosarcoma patients was further evaluated.

Results

RT-PCR and Western blot assays revealed that NRP-1 expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues at both mRNA and protein levels (both P < 0.001). In addition, high NRP-1 expression more frequently occurred in osteosarcoma tissues with advanced clinical stage (P = 0.006), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.006). Moreover, osteosarcoma patients with high NRP-1 expression had significantly shorter overall survival and disease-free survival (both P < 0.001) when compared with patients with the low expression of NRP-1. On Cox multivariate analysis, NRP-1 overexpression was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both P = 0.001).

Conclusion

This is the first study to reveal that NRP-1 overexpression may be related to the prediction of metastasis potency, response to chemotherapy and poor prognosis for osteosarcoma patients, suggesting that NRP-1 may serve as a prognostic marker for the optimization of clinical treatments.     

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P?=?0.019), clinical stage (P?=?0.001), and lymph node metastasis (P?=?0.026). The Kaplan–Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.     

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.     

High Expression of Neuropilin-1 Associates with Unfavorable Clinicopathological Features in Hepatocellular Carcinoma

As a co-receptor for vascular endothelial growth factor (VEGF), Neuropilin-1 (NRP-1) plays an important role in angiogenesis and malignant progression of many human cancers. However, the role of NRP-1 in hepatocellular carcinoma (HCC) is not well understood. The study aimed to detected the expression of Neuropilin-1 in HCC and investigate the association between its expression and the clinicopathological characteristics and prognosis of HCC. Quantitative real-time PCR (qRT-PCR), Western blot, Immunofluorescence and immunohistochemistry (IHC) analyses were performed to characterize the expression of NRP-1 in HCC cell lines and tissues. The association of NRP-1 expression with the clinicopathological characteristics and the prognosis was subsequently assessed. qRT-PCR and Western blot assays revealed that the expression of NRP-1 in HCC was significantly increased relative to that of normal live cells and tissues (P < 0.05,and <0.001, respectively). In addition, high expression of NRP-1 was significantly associated with intrahepatic metastasis (P = 0.036), Edmondson grade (P = 0.007), TNM classification (P = 0.0031), and portal vein invasion (P = 0.004). Furthermore, the HCC patients with high NRP-1 expression had shorter overall survival (OS), and recurrence-free survival (RFS), whereas, patients with low NRP-1 expression had better OS and RFS (P = 0.0035, and 0.0048, respectively). These data indicate that NRP-1 expression may play an important role in the progression of HCC, and that high NRP-1 expression suggests unfavorable clinicopathological characteristics and survival in HCC patients.     

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.     

Overexpression of MACC1 protein and its clinical implications in patients with glioma

Metastasis associated in colon cancer 1 (MACC1) has been regarded as a novel potential therapeutic target for multiple cancers. However, the impact of MACC1 in glioma remains unclear. The aim of this study was to analyze the correlation of MACC1 expression with the clinicopathological features of glioma. MACC1 mRNA and protein expression levels in human glioma tissues were detected by quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. MACC1 mRNA and protein expression were both significantly higher in glioma tissues than in corresponding noncancerous brain tissues (both P?<?0.001). In addition, statistical analysis suggested that high MACC1 expression was significantly correlated with advanced pathological grade (P?=?0.004) and that patients with high expression of MACC1 protein exhibited a poorer prognosis than those with low MACC1 expression. Furthermore, Cox multivariate analysis showed that MACC1 overexpression was an independent prognostic factor for predicting the overall survival of glioma patients. In conclusion, expression of MACC1 in glioma could be adopted as a candidate biomarker for the diagnosis of clinical stage and for assessing prognosis, indicating for the first time that MACC1 may play an important role in the tumor development and progression in glioma. MACC1 might be considered as a novel therapeutic target against this 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.     

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.     

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.     

Prognostic Significance of Beclin-1 Expression in Laryngeal Squamous Cell Carcinoma

Beclin-1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The aim of the present investigation was to analyze the Beclin-1 protein expression and to assess its prognostic significance in tissue of laryngeal squamous cell carcinoma (LSCC). Beclin-1 protein expression in 82 primary laryngeal squamous cell carcinoma and 40 paracarcinoma non-tumor tissue samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients’ outcome. The expression of Beclin-1 in tumor tissues was significantly lower than that in non-tumor tissues (P?=?0.035). Reduced Beclin-1 expression was significantly correlated with lymph node metastases (P?=?0.021). Kaplan–Meier survival estimates showed a significant correlation between Beclin-1 expression and patient’s survival rate (log-rank P?<?0.05). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P?=?0.048) and Beclin-1 expression (P?=?0.029) were statistically significant, independent prognostic factors for LSCC. Our findings suggested that decreased Beclin-1 expression and lymph node metastases, as examined by immunohistochemistry, are both independent biomarker for poor prognosis of patients with LSCC.     

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.