A gene mutation in RNA-binding protein 10 is associated with lung adenocarcinoma progression and poor prognosis

RNA 结合蛋白 10 基因突变与肺腺癌进展和不良预后相关

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作者:Lin-Lin Yin, Xin-Mian Wen, Ming Li, Yan-Mei Xu, Xiao-Feng Zhao, Jing Li, Xiu-Wen Wang

Abstract

RBM10 regulates the expression of various genes, which are often mutated in male lung adenocarcinoma. The present study confirmed the association of the RBM10 mutation at exon 10 with the clinicopathological data and prognosis of lung adenocarcinoma. The effect of mutant RBM10 on regulating lung cancer cell growth and invasion was investigated in vitro. Tissue specimens from 50 patients with lung adenocarcinoma were subjected to Sanger sequencing for RBM10 exon 10 mutations. Lung adenocarcinoma cells were transfected with pcDNA3.1 carrying wild type RBM10 cDNA or exon mutation cDNA for cell viability, apoptosis and invasion assays. RBM10 exon 10 mutations were identified in 11 out of 50 patients, with a high frequency in male patients [c.763 C>T, p.Arg241Cys for 33.3% (10/30)] and were significantly associated with the American Joint Committee on Cancer stage (P=0.005), lymph node metastasis (P=0.019) and shorter 5-year survival rate compared with the wild type RBM10 (36.4% vs. 46.5%; P=0.019). Multivariate analysis revealed that RBM10 exon 10 mutation was an independent prognostic factor (HR=3.787; P=0.033). RBM10 exon 10 mutation at c.763 C>T significantly promoted tumor cell proliferation and invasion capacity, whereas wild type RBM10 inhibited tumor cell invasion in vitro. In conclusion, RBM 10 mutation at exon 10 (c.763 C>T) occurs frequently and is an independent prognostic predictor in lung adenocarcinoma.

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