CDC20 and PTTG1 are Important Biomarkers and Potential Therapeutic Targets for Metastatic Prostate Cancer.

INTRODUCTION: Metastatic prostate cancer (mPCa) is responsible for most prostate cancer (PCa) deaths worldwide. The present study aims to explore the molecular differences between mPCa and PCa. METHODS: The authors downloaded GSE6752, GSE6919, and GSE32269 from the Gene Expression Omnibus and employed integrated analysis to identify differentially expressed genes (DEGs) between mPCa and PCa. Functional and pathway-enrichment analyses were performed, and a protein-protein interaction (PPI) network and modules were constructed. Clinical mPCa specimens were collected to verify the results by performing RT-qPCR. The Cancer Genome Atlas database was used to conduct a survival analysis, and an immunohistochemical assay was performed. The invasion ability of PCa cells was verified by Transwell assay. RESULTS: One-hundred six consistently DEGs were found in mPCa compared with PCa. DEGs significantly enriched the positive regulation of cell proliferation, cell division, and cell adhesion in small cell lung cancer and PCa. Cell division, nucleoplasm, and cell cycle were selected from the PPI network, and the top 10 hub genes were selected. CDC20 and PTTG1 with genetic alterations were significantly associated with poorer disease-free survival. Immunohistochemical assay results showed that the expression levels of CDC20 and PTTG1 in mPCa were higher than those in PCa. The results of the migration assay indicated that CDC20 and PTTG1 could enhance the migration ability of PCa cells. CONCLUSION: The present study revealed that CDC20 and PTTG1 contribute more to migration, progression, and poorer prognoses in mPCa compared with PCa. CDC20 and PTTG1 could represent therapeutic targets in mPCa medical research and clinical studies.

Hypoxia upregulates HIG2 expression and contributes to bevacizumab resistance in glioblastoma.

Hypoxia contributes to the maintenance of stem-like cells in glioblastoma (GBM), and activates vascular mimicry and tumor resistance to anti-angiogenesis treatments. The present study examined the expression patterns and biological significance of hypoxia-inducible protein 2 (HIG2, also known as HILPDA) in GBM. HIG2 was highly expressed in gliomas and was correlated with tumor grade, and high HIG2 expression independently predicted poor GBM patient prognosis. HIG2 was upregulated during hypoxia and by hypoxia mimics, and HIG2 knockdown in GBM cells inhibited cell proliferation and invasion. HIF1α bound to the HIG2 promoter and increased its expression in GBM cells, and HIG2 upregulated HIF1α expression. Reconstruction of a HIG2-related molecular network using bioinformatics methods revealed that HIG2 is closely correlated with angiogenesis genes, such as VEGFA, in GBM. HIG2 levels positively correlated with VEGFA in GBM samples. In addition, treatment of transplanted xenograft nude mice with bevacizumab (anti-angiogenesis therapy) resulted in HIG2 upregulation at late stages. We conclude that HIG2 is overexpressed in GBM and upregulated by hypoxia, and is a potential novel therapeutic target. HIG2 overexpression is an independent prognostic indicator and may promote tumor resistance to anti-angiogenesis treatments.

[Expression and clinical significance of E-cadherin and ß-catenin in the vulvar squamous cell carcinoma tissues].

OBJECTIVE: To investigate the expression of E-cadherin and ß-catenin in the Vulvar squamous cell carcinoma (VSCC) tissues. METHODS: A total of 63 documented paraffin blocks of VSCC (n=41), vulvar intraepithelial neoplasia (n=22), vulvar negative cutting edge tissues (n=10) diagnosed in department of pathology of Shengjing Hospital of China Medical University from January 2005 to April 2012 were enrolled. EliVision immunohistochemical staining was used to detect the expression of E-cadherin and ß-catenin in the three groups. Then to do a statistical analysis among the expression of them with patients' menopause status, pathological grade, clinical stage and lymph node metastasis. Spearman correlation analysis was used to analyse the expression of E-cadherin and ß-catenin in the vulvar lesion tissues. RESULTS: The abnormal immunoreactivity for E-cadherin [46%(19/41), 64% (14/22)] and ß-catenin [61% (25/41), 68% (15/22)] in VSCC and VINII-III were found, which were significantly different from that in normal epithelium samples (P<0.05). The abnormal expression of E-cadherin and ß-catenin have no statistically significant difference between VSCC group and VINII-III group (P>0.05). The abnormal expression of E-cadherin and ß-catenin were collected with tumor pathological grade and lymph node metastasis status (all P<0.05). The abnormal expression of E-cadherin and ß-catenin have no statistically significant difference between menopause and the surgical stage of patients (all P>0.05). The abnormal expression of E-cadherin and ß-catenin have a significant positive correlation in the same sample in the VSCC tissue (r=0.543, P=0.000). The abnormal expression of E-cadherin and ß-catenin have no correlation in the VINII-III tissue (r=0.295, P=0.182). CONCLUSIONS: The abnormal expression of E-cadherin and ß-catenin may occurs frequently in the VSCC. The abnormal expression of E-cadherin and ß-catenin have correlation with vulvar cancer pathological grade and lymph node metastasis, which may be important mechanisms promoting the invasion and metastasis of VSCC.