Overexpression of osteopontin independently correlates with vascular invasion and poor prognosis in patients with hepatocellular carcinoma

This study retrospectively evaluated the immunohistochemical expression of 3 cell adhesion molecules (CAMs), E-cadherin, beta-catenin, and osteopontin, according to tumor grade in 125 surgically resected specimens of hepatocellular carcinoma (HCC). The aims of this study were to identify factors associated with vascular invasion and to elucidate the prognostic value of CAMs. The median follow-up time was 110 months. The levels of E-cadherin, beta-catenin, and osteopontin immunoreactivity were significantly associated with Edmondson-Steiner grade but not with tumor size. There was increased loss of E-cadherin, nonnuclear overexpression of beta-catenin, and overexpression of osteopontin in tumors of higher histologic grade. Vascular invasion was found in 44 (35%) of 125 resected specimens. Logistic regression analysis identified 3 tumor-related factors that were independently associated with vascular invasion-tumor size more than 3 cm, Edmondson-Steiner grades III to IV, and overexpression of osteopontin. Among the tested CAMs, osteopontin (P = .0110) and E-cadherin (P = .0287) were significant prognostic factors by univariate analysis. The Cox proportional hazard regression analysis revealed that Edmondson-Steiner grades III to IV (relative risk [RR], 3.028; P < .001), the presence of vascular invasion (RR, 1.964; P = .011), overexpression of osteopontin (RR, 1.755; P = .034), serum alpha-fetoprotein level more than 20 ng/mL (RR, 1.834; P = .037), and Child-Pugh classification B to C (RR, 1.880; P = .040) were found to be independently significant factors associated with survival after hepatectomy. These results suggest that overexpression of osteopontin independently correlates with vascular invasion and thus predicts poor survival for patients with HCC, whereas aberrant expression of E-cadherin or beta-catenin does not.     

Decreased expression of serum miR-424 correlates with poor prognosis of patients with hepatocellular carcinoma

Background: MicroRNAs (miRNAs) play important roles in many important cellular processes and deregulation of miRNAs is linked to many human diseases including cancer. Although miR-424 has been demonstrated to inhibit progression of hepatocellular carcinoma (HCC), its expression level in serum samples and the potential clinical values remain unknown. Materials and methods: The expression level of miR-424 in the serum clinical samples from HCC patients and healthy volunteers were determined by qRT-PCR. Then the association of serum miR-424 expression level with various important clinicopathological parameters and survival rates was evaluated. Multivariate Cox regression analysis was used to identify the independent risk factors for HCC. Results: The expression level of serum miR-424 was significantly decreased in patients with HCC compared with the healthy volunteers (P<0.01). Reduced expression of serum miR-424 was associated with serum AFP (P=0.048), vein invasion (P=0.006) and TNM stage (P=0.003). In addition, survival analysis showed that HCC patients with lower serum miR-424 expression suffered poorer overall survival (P=0.018) and disease free survival (P=0.008). Moreover, serum miR-424 was demonstrated to be an independent risk factor for HCC. Conclusions: Our findings provide the compelling evidence that the decreased expression of serum miR-424 may serve as a novel biomarker to predict the unfavorable prognosis of HCC patients.     

High expression of CRAM correlates with poor prognosis in patients with cervical carcinoma

Aims: Atypical chemokine receptors (ACRs) have been reported to scavenge or alter the localization of their chemokine ligands. However, CRAM, a newly identified ACR member, is lack of ligand scavenging properties. The present study was to investigate the clinical significance of CRAM in cervical carcinoma. Methods: The expression of CRAM in primary cervical cancer and paired normal tissues from adjacent regions was examined using Real time PCR. Moreover, CRAM protein expression was analyzed in 272 cervical specimens including 50 normal cervical tissues, 40 cases of carcinoma in situ of cervix (CIS), and 182 cases of cervical cancer by immunohistochemistry. Results: Real time PCR showed that the expression level of CRAM was markedly higher in cervical cancer than that in normal cervical tissues. The expression rate of CRAM in normal cervical tissues, CIS, and cervical cancer increased gradually (p < 0.01). In addition, the expression level of CCL19 was positively associated with that of CRAM (p < 0.05). Moreover, high expression level of CRAM was correlated with lymph node metastasis and histological subtype. In multivariate Cox regression analysis, high expression level of CRAM was a negative indicator for both overall (p = 0.028) and recurrence-free survival (p = 0.010). Conclusion: The present study suggested that CRAM could be a clinical prognostic marker for patients with cervical cancer and might be a potential therapeutic target for cervical cancer. Our data extended previous research on the predictive value of ACRs.     

Elevated Mortalin correlates with poor outcome in hepatocellular carcinoma

Although several lines of evidence existed suggesting that Mortalin was linked with survival in malignant tumors; it has been barely described regarding the prognostic involvement of its expression in hepatocellular carcinoma (HCC). Herein, to understand the prognostic meaning of Mortalin expression, Immunohistochemistry was undertaken to observe the immunohistochemical characteristics of Mortalin on HCC tissue microarray consisting of 90 cases of HCC and its paired normal control dots, followed by detailed statistical analysis with the accompanying clinicopathological variables available, including gender, age, tumor size, differentiation, cirrhosis, vascular invasion, clinical stage, T classification and intrahepatic metastases. Meanwhile, Kaplan-Meier survival curve was plotted to analyze the prognostic difference for patients with high and low expression of Mortalin. It was exhibited that Mortalin was over-expressed in HCC tissues relative to paired normal control and elevated Mortalin significantly correlated with vascular invasion, clinical stage and intrahepatic metastasis. Kaplan-Meier survival analysis revealed that Mortalin was remarkably associated with overall survival and disease-free survival. Multivariate Cox regression analysis showed that expression of Mortalin was an independent prognostic factor in HCC. Collectively, the data we provided here support the prognostic prediction value of Mortalin in HCC.     

Increased expression of miR-21 predicts poor prognosis in patients with hepatocellular carcinoma

Background: MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC) development and progression. Aberrant miR-21 expression has been reported in several cancers. However, the clinical significance of miR-21 in human HCC is still unclear. Methods: A total of 112 patients with primary HCC who underwent a curative liver resection were included in this retrospective study. The differentially expressed amount of the miR-21 was validated by quantitative real-time PCR (qRT-PCR). Survival rate was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Multivariate analysis of the prognostic factors was performed with Cox regression model. Results: As revealed by qRT-PCR analysis, miR-21 expression was significantly upregulated in HCC tissues when compared with adjacent non-tumor tissues (P<0.05). High miR-21 expression level was observed to be closely correlated with tumor differentiation, TNM stage and vein invasion (P<0.05). Patients who had high miR-21 expression had a shorter overall survival than patients who had low miR-21 expression (P<0.05). Moreover, multivariate analysis of the prognosis factors with a Cox proportional hazards model showed that high miR-21 expression was a significant independent predictor of poor survival in HCC (P<0.05). Conclusion: Our results suggested that increased expression of miR-21 was significantly correlated with tumor progression and could be a novel potential biomarker for HCC prognosis.     

High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma

Background  

It has been suggested that p300 participates in the regulation of a wide range of cell biological processes and mutation of p300 has been identified in certain types of human cancers. However, the expression dynamics of p300 in hepatocellular carcinoma (HCC) and its clinical/prognostic significance are unclear.     

High RSF-1 expression correlates with poor prognosis in patients with gastric adenocarcinoma

Aim

To investigate the expression and prognostic significance of RSF-1 in gastric adenocarcinoma.

Methods

RSF-1 expression was analyzed using immunohistochemical staining on tissue samples from a consecutive series of 287 gastric adenocarcinoma patients who underwent tumor resections between 2003 and 2006.The relationship between RSF-1 expression, clinicopathological factors, and patient survival was investigated.

Results

Immunohistochemical staining indicated that RSF-1 is highly expressed in 52.6% of gastric adenocarcinomas. RSF-1 expression levels were closely associated with tumor size, histological differentiation, tumor stage, and lymph node involvement. Kaplan-Meier survival analysis showed that high RSF-1 expression exhibited a significant correlation with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis revealed that RSF-1 expression is an independent prognostic parameter for the overall survival rate of gastric adenocarcinoma patients.

Conclusion

Our data suggest that RSF-1 plays an important role in gastric adenocarcinoma progression and that high RSF-1 expression predicts an unfavorable prognosis in gastric adenocarcinoma patients.     

Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma

CB1 and CB2 are multifunctional cannabinoid-specific receptors considered to be involved in inhibition of tumor development. To elucidate their roles in hepatocarcinogenesis, we analyzed the expression of these receptors in tumor and matched nontumorous tissues of human hepatocellular carcinoma (HCC) samples. In situ hybridization analysis showed overexpression of CB1 mRNAs in 8 of 13 (62%) HCC samples, and of CB2 mRNAs in 7 of 13 (54%). Immunohistochemical analysis of 64 HCC samples showed the expression of CB1 and CB2 receptors to increase from normal liver to chronic hepatitis to cirrhosis. Marked expression of CB1 and CB2 receptors was noted in the majority of cirrhotic liver samples (86 and 78%, respectively). In HCC, high expression of CB1 and CB2 receptors was observed in 29 (45%) and 33 (52%) cases, respectively. Clinicopathological evaluation indicated a significant correlation between CB1 and CB2 expression and two clinicopathological parameters such as the histopathological differentiation (P = 0.021 and 0.001, respectively), portal vein invasion (P = 0.015 and 0.004, respectively). Univariate analysis indicated that disease-free survival was significantly better in HCC patients with high versus those with low CB1 and CB2 expression levels (P = 0.010 and 0.037, respectively). Our results indicate that CB1 and CB2 have potential as prognostic indicators and suggest possible beneficial effects of cannabinoids on prognosis of patients with HCC.     

Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma.

Liver is the primary source for collagen XVIII, the precursor of angiogenesis inhibitor, endostatin. However, the role of endostatin/collagen XVIII expression during liver carcinogenesis remains elusive. Therefore, we studied its expression in five hepatoma cell lines and 105 hepatocellular carcinoma specimens. The poorly differentiated hepatoma cell lines exhibited increased endostatin/collagen XVIII levels compared with the well-differentiated ones. In hepatoma tissues, endostatin/collagen XVIII expression was detected in various types of liver cells and was significantly stronger in adjacent nontumor tissues than that in tumors (P<0.001). Endostatin/collagen XVIII expression in nontumor tissues correlated with tumor stages (P=0.014) and expression of vascular endothelial growth factor (P=0.007), but not the stages of hepatic fibrosis (P>0.05). Kaplan-Meier analysis showed that patients with higher endostatin/collagen XVIII expression had significantly shorter overall survival (P=0.011) and disease-free survival (P=0.0034). Moreover, endostatin/collagen XVIII level was an independent prognostic factor for tumor recurrence (P=0.034) by multivariate analysis. In conclusion, increased endostatin/collagen XVIII expression correlated with hepatoma progression and predicted poor prognosis for patients with hepatocellular carcinoma.     

Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis

Background: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA Sox2ot is up-regulated in some tumors. However, the contributions of Sox2ot to hepatocellular carcinoma (HCC) remain largely unknown. Methods: In the present study, expression of lncRNA Sox2ot was evaluated by quantitative real-time PCR in tumor tissues and adjacent non-tumor tissues in 84 HCC patients. The association of lncRNA Sox2ot expression with clinicopathological features and the prognosis of HCC patients were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox’s proportional hazards model. Small interfering RNA assay was used to explore the function of lncRNA Sox2ot on HCC cell migration and invasion. Results: lncRNA Sox2ot expression level was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.05). High expression of lncRNA Sox2ot was associated with histological grade, TNM stage, and vein invasion. The 5-year overall survival of high lncRNA Sox2ot expression group was significantly shorter than that of low lncRNA Sox2ot expression group (P<0.05). The multivariate Cox regression analysis indicated that lncRNA Sox2ot expression was an independent prognostic factor for overall survival. In addition, the metastasis ability of HCC cells was significantly decreased by knocking down lncRNA Sox2ot expression. Conclusions: The results suggested that lncRNA Sox2ot played crucial roles in promoting HCC cell migration and invasion, and might represent a novel prognostic biomarker for HCC.     

Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma

Luo W‐R, Wu A‐B, Fang W‐Y, Li S‐Y & Yao K‐T (2012) Histopathology  61, 237–246 Nuclear expression of N‐cadherin correlates with poor prognosis of nasopharyngeal carcinoma Aims: To investigate the aberrant expression of N‐cadherin in nasopharyngeal carcinoma (NPC) and its prognostic significance. Methods and results: Immunohistochemical staining for N‐cadherin protein was performed on tissue microarray (TMA) from 122 NPC patients. Cytoplasmic N‐cadherin was observed in 42.6% and nuclear N‐cadherin in 45.1% of NPC tissues. High expression of cytoplasmic and nuclear N‐cadherin was associated with a majority of the clinicopathological variables, including lymph node metastasis, distant metastasis and clinical stage. Cytoplasmic N‐cadherin was associated positively with nuclear N‐cadherin expression (P = 0.000). In univariate analysis, cytoplasmic N‐cadherin showed no significant impact on patient prognosis. In contrast, the overall survival was significantly shorter in patients with high nuclear N‐cadherin than those with low levels of staining (P = 0.002). A high expression of nuclear N‐cadherin predicted poorer survival in patients with late stage disease (P = 0.033), but not those with early tumour stage. In addition, multivariate analysis showed nuclear N‐cadherin to bean independent prognostic marker for NPC patients (P = 0.024). Conclusions: Nuclear N‐cadherin expression may represent a valuable prognostic marker in NPC patients, especially those with late stage disease.     

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.     

CREPT expression correlates with poor prognosis in patients with retroperitoneal leiomyosarcoma

Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People’s Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P < 0.001 and P = 0.009, respectively). Multivariate analysis showed that survival was associated with histological grade and the expression level of CREPT (P = 0.011 and P = 0.012, respectively). Kaplan-Meier analysis showed that the patients lacking CREPT expression exhibited significantly longer overall postoperative survival (median, 60.0 months) than the patients displaying CREPT expression (median, 33.0 months), and CREPT expression correlated with distant recurrence within 5 years after surgery (P = 0.004). Western blot analyses showed that CREPT was more strongly expressed in the retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers.     

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.