HOXA10­AS: A novel oncogenic long non­coding RNA in glioma.

Glioma is the most common primary malignant tumor of the central nervous system. Emerging evidence has demonstrated that long non­coding RNAs (lncRNAs) serve a major role of regulation in various types of human cancer, including glioma. However, the biological roles of thousands of lncRNAs remain unknown and require further identification. The present study investigated the functional role of lncRNA­HOXA10­AS in glioma. The present study examined the expression patterns of HOXA10­AS in glioma and normal brain tissues, as well as glioma cell lines and normal human astrocytes (HA) via reverse transcription­quantitative polymerase chain reaction. HOXA10­AS knockdown cells were generated using lentiviral short hairpin RNA against HOXA10­AS in A172 and U251 glioma cells. Cell growth was assessed by MTT assay, and a flow cytometer was used to investigate cell proliferation, cell cycle distribution and cell apoptosis. Western blot analysis was performed to analyze the expression levels of apoptosis­related proteins. HOXA10­AS was significantly upregulated in glioma tissues and cell lines, and increased HOXA10­AS expression levels were associated with higher grades of glioma. Knockdown of HOXA10­AS inhibited glioma cell proliferation and increased cell apoptosis rates compared with the control cells. HOXA10­AS markedly regulated the expression of the homeobox A10 (HOXA10) gene. Similarly, HOXA10 expression was increased with higher grades of glioma, and silencing of HOXA10 by small interfering RNA suppressed glioma cell proliferation and induced cell apoptosis. The results of the present study demonstrated that HOXA10­AS promoted cell growth and survival through activation of HOXA10 gene expression in glioma, which may potentially act as a novel biomarker and therapeutic target for clinical assay development.

KRAS Mutation as a Biomarker for Survival in Patients with Non-Small Cell Lung Cancer, A Meta-Analysis of 12 Randomized Trials.

BACKGROUND: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. MATERIALS AND METHODS: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. RESULTS: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). CONCLUSIONS: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.