The Clinical and Prognostic Implications of Pluripotent Stem Cell Markers Expression and Their Correlation with the WNT signal pathway in Hepatocellular Carcinoma.

OBJECTIVES: This study aimed to investigate the expression of SOX2, SOX9, p53, and ß-catenin in hepatocellular carcinoma (HCC) and their correlation with clinicopathological parameters of prognostic importance. MATERIALS AND METHODS: Seventy-five patients were enrolled in this study. All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors and patient survival. RESULTS: We detected the positive expression of SOX2, SOX9, p53, and ß-catenin in 76%, 50.7%, 50.7%, and 77.9% of HCC specimens respectively. All studied markers showed a significant increase in the expression in tumor tissue specimens compared to non-tumor tissue. Both SOX2 and SOX9 expressions were significantly associated with adverse prognostic factors in HCC. Significant positive correlations were found between SOX2 and SOX9 and both p53 and ß-catenin expression (r= 0.528, 0.485 and; r = 0.253, 0.327, respectively; p < 0.0001 for both of them). Regarding survival, we found that HCC patients with positive SOX2 and SOX9 expressions had significantly shorter overall survival (p=0.0001, each). Additionally, larger tumor size, tumor grade, high stage, tumor multiplicity, presence of cirrhosis, tumor necrosis, high p53 expression, and positive ß-catenin expression were independent predictors of worse survival. A multivariate Cox analysis revealed that tumor grade, stage, p53, and SOX2 expression were independent predictors of unfavorable prognosis in overall survival (p=0.0001, p=0.0001,p=0.033; and p=0.003, respectively). CONCLUSIONS: Our findings might provide an insight into SOX2 and SOX9's role in HCC and suggest that SOX2 might be targeted for HCC therapy.

Golgi Phosphoprotein-3 and Y-Box-Binding Protein-1 Are Novel Markers Correlating With Poor Prognosis in Prostate Cancer.

BACKGROUND: Prostate cancer is a common and aggressive cancer among men. Despite advances in treatment, the mechanisms involved in progression are still unclear. New prognostic markers are needed to better design patient-specific therapeutic regimens. MATERIALS AND METHODS: The present study included 120 patients: 76 with prostate carcinoma, 12 with low-grade prostate intraepithelial lesions, 12 with high-grade prostate intraepithelial lesions, and 20 with benign prostatic hyperplasia. Immunohistochemical study was performed for Golgi phosphoprotein-3 (GOLPH3) and Y-box-binding protein-1 (YB-1) analysis. The correlation with clinicopathologic data and overall survival was analyzed. RESULTS: Both GOLPH3 and YB-1 showed increased expression from benign to malignant tumors. In prostate carcinoma, cytoplasmic GOLPH3 was associated with Gleason score, tumor stage, and androgen receptor status (P = .034, P < .001, and P = .008, respectively). Nuclear YB-1 expression was associated with Gleason score and androgen receptor status (P = .018 and P = .024, respectively). Cytoplasmic YB-1 expression was associated with Gleason score, tumor stage, and androgen receptor status (P = .008, P = .027, and P < .001, respectively). A high Gleason score (P = .004), high tumor stage (P < .001), and androgen receptor-independent cancer (P = .006) were the only detected adverse prognostic clinicopathologic factors. Moderate to intense GOLPH3 and high nuclear and cytoplasmic YB-1 expression correlated with shorter overall survival (P < .001, P = .020, and P < .001, respectively). On multivariate analysis, moderate to intense GOLPH3 expression was the only predictor of overall survival (P = .025). CONCLUSION: High GOLPH3 and nuclear/cytoplasmic YB-1 expression correlated with a poor prognosis in patients with prostate cancer. Both markers could be promising targets for new treatment strategies.

Defective Beclin-1 and elevated hypoxia-inducible factor (HIF)-1α expression are closely linked to tumorigenesis, differentiation, and progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. Autophagy and hypoxia have been involved in HCC tumorigenesis. In the present study, we examined the relationship between Beclin-1 expression and hypoxia-inducible factor (HIF)-1α expression in HCC by immunohistochemistry on 65 tumor specimens. Their correlations with clinicopathological features were also explored. There was a loss of Beclin-1 protein expression in 49.2 % of HCC. Beclin-1 expression was only significantly correlated with virus infection status (p = 0.025) and marginally associated with HCC grade (p = 0.057). Forty-two tumors (64.6 %) showed high HIF-1α expression, and it was significantly associated with large tumor size (p = 0.003), multifocal tumors (p = 0.038), and advanced stage (p = 0.043). Beclin-1 expression was significantly associated with HIF-1α expression (p = 0.001). HCC cases were further stratified according to their hypoxia status into hypoxic and normoxic groups. In the hypoxic group, Beclin-1 expression was negatively correlated with HCC high tumor grade (p < 0.001), advanced stage (p = 0.013), large size (p = 0.002), and multifocal tumors (p = 0.047). In the normoxic group, no significant relations between Beclin-1 expression and any of the clinicopathological parameters were identified. Our findings that reduced Beclin-1 and high HIF-1α expression are associated with the development and progression of HCC may provide molecular therapeutic targets toward inhibiting HCC development and progression.

GOLPH3 and YB-1 Are Novel Markers Correlating With Poor Prognosis in Prostate Cancer.

BACKGROUND: Prostate cancer is a common and aggressive cancer among men. Despite advances in the treatment, the mechanisms involved in progression are still unclear. New prognostic markers should be explored for better design of patient-specific therapeutic regimens. METHODS: This study was performed on 120 patients stratified as 76 with prostatic carcinoma, 12 with low-grade prostate intraepithelial lesion, 12 with high-grade prostate intraepithelial lesion and 20 with benign prostate hyperplasia. Immunohistochemical study was done for Golgi phosphoprotein 3 (GOLPH3) and Y-box binding protein-1 (YB-1) analysis. Correlation with clinicopathological data and overall survival was analyzed. RESULTS: Both GOLPH3 and YB-1 showed increased expression from benign to malignant tumors. In prostatic carcinoma, cytoplasmic GOLPH3 was associated with Gleason score, stage and androgen receptor (P = 0.034, P < 0.001, and P = 0.008 respectively). Nuclear YB-1 expression was associated with Gleason score and androgen receptor (P = 0.018 and P = 0.024 respectively). Cytoplasmic YB-1 expression was associated with Gleason score, stage and androgen receptor (P = 0.008, P = 0.027, and P < 0.001 respectively). High Gleason score (P = 0.004), high stage (P < 0.001) and androgen receptor (P = 0.006) were the only detected adverse prognostic clinicopathological factors. Moderate/intense GOLPH3 and high nuclear and cytoplasmic YB-1 expression were correlated with shorter overall survival (P < 0.001, P = 0.020, and P < 0.001 respectively). In the multivariate analysis, moderate/intense GOLPH3 expression was the only predictor of overall survival (P = 0.025). CONCLUSIONS: High GOLPH3 and nuclear/cytoplasmic YB-1 expression correlated with poor prognosis in prostate cancer. Both markers can be promising targets for new treatment strategies.

Expression of a disintegrin and metalloprotease 8 and endostatin in human osteosarcoma: implication in tumor progression and prognosis.

BACKGROUND: A disintegrin and metalloprotease 8 (ADAM8) is a trans-membrane protein, which is involved in cell adhesion, signaling and migration as well as the proteolytic cleavage of various substrates. Endostatin is a potent inhibitor of angiogenesis. ADAM8 and Endostatin have been associated with multiple malignancies. However, their role in osteosarcoma is not fully elucidated. AIM: To determine the expression of ADAM8 and endostatin in osteosarcoma and to study their correlation with different clinicopathological parameters and patients' outcomes. MATERIAL AND METHODS: ADAM8 and endostatin expression were immunohistochemically evaluated in 61 primary osteosarcomas and 11 pulmonary metastatic osteosarcoma lesions. RESULTS: Among 61 primary osteosarcomas, ADAM8 was detected in 52 tumors (85.2%) and highly expressed in 33 cases (54.1%). Positive endostatin expression was found in 28 tumors (45.9%). Higher ADAM8 and decreased endostatin expression rates in metastatic lesions compared to primary osteosarcoma were found but these differences were not statistically significant (p=0.086 & 0.558 respectively). High ADAM8 expression score and positive endostatin expression were significantly correlated with tumor size, stage and distant metastasis (p<0.05). Survival analysis showed that high ADAM8 expression was associated with poor overall survival (OS) (p=0.0002). Multivariate analysis revealed that ADAM8 expression level was an independent prognostic parameter for the OS (p=0.017). CONCLUSION: Our data suggest that ADAM8 and endostatin play a role in osteosarcoma progression. High ADAM8 expression serves as a reliable marker for poor prognosis in osteosarcoma patients.