hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer.

PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT.

MAGI1 Inhibits the Proliferation, Migration and Invasion of Glioma Cells.

BACKGROUND: Membrane-associated guanylate kinase inverted repeat member 1 (MAGI1) acts as a tumor suppressor in a variety of tumors; however, its expression and biological function in glioma are still unknown. METHODS: MAGI1 expression in glioma was examined by immunohistochemistry. In addition, overexpression of MAGI1 in U87 and U373 cells, colony formation and MTT assays were used to evaluate cell proliferation, Transwell assays to determine cell migration and invasion, and a xenograft model established using U87 cells to evaluate the effect of MAGI1 overexpression in vivo. Western blot assays were used to analyze the Akt, MMP2, MMP9 and E-cadherin/N-cadherin/vimentin pathway changes after overexpression of MAGI1. RESULTS: We demonstrated that MAGI1 was expressed at low levels in glioma. Low MAGI1 expression was positively correlated with the malignant progression of glioma and indicated a poor prognosis. Moreover, we found that overexpressed MAGI1 inhibited the proliferation, migration and invasion of glioma cells by regulating cell growth and EMT through Akt, MMP2, MMP9 and the E-cadherin/N-cadherin/vimentin pathway. CONCLUSION: These findings demonstrate a novel function of MAGI1 in glioma progression and suggest that MAGI1 might be a target for the diagnosis and treatment of glioma.

Prognostic and clinicopathological significance of CCAT2 in Chinese patients with various tumors.

BACKGROUND: Colon cancer-associated transcript 2 (CCAT2) as a long noncoding RNA (lncRNA) is overexpressed and plays a significant prognostic role in patients with tumors. The present study aimed to comprehensively evaluate the clinical value of CCAT2 in the Chinese population, as a potential prognostic marker in multiple cancers. METHODS: A systematic search of eligible studies was conducted in the PubMed, Web of Science, Cochrane Library, Wanfang and the China National Knowledge Infrastructure databases as of March 31, 2017. Approximately 1,711 tumor patients from 16 eligible studies were selected. Analyses of the pooled data were performed, and the odds ratio (OR) or hazard ratio (HR) and the 95% confidence interval (95% CI) were calculated and summarized to evaluate the strength of this association using a fixed- or random-effects model. RESULTS: Overall analyses showed that increased CCAT2 expression was associated with a higher risk of lymph node metastasis (LNM), an increased potential for distant metastasis (DM) and higher clinical stage (p<0.001 for LNM, p = 0.001 for DM, p<0.001 for clinical stage). HR and the 95% CI for overall survival (OS) were assessed to pool the effect size using a fixed-effects model. A significant association was observed between increased CCAT2 expression and poor OS (pooled HR = 1.91, 95% CI, 1.63-2.22, p<0.001). CONCLUSIONS: These results indicate that CCAT2 is a biomarker to predict tumor progression and a potential prognostic marker in multiple cancers. Additional well-designed clinical studies are needed to validate these findings.

Prognostic Role of the Pretreatment C-Reactive Protein/Albumin Ratio in Solid Cancers: A Meta-Analysis.

The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58-2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients.