Yin Lin-Lin, Wen Xin-Mian, Li Ming, Xu Yan-Mei, Zhao Xiao-Feng, Li Jing, Wang Xiu-Wen
Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong 250000, P.R. China.
Department of Hematology and Oncology, The Fourth Hospital of Jinan, Jinan, Shandong 250031, P.R. China.
Oncol Lett. 2018 Nov;16(5):6283-6292. doi: 10.3892/ol.2018.9496. Epub 2018 Sep 24.
RBM10 regulates the expression of various genes, which are often mutated in male lung adenocarcinoma. The present study confirmed the association of the mutation at exon 10 with the clinicopathological data and prognosis of lung adenocarcinoma. The effect of mutant on regulating lung cancer cell growth and invasion was investigated . Tissue specimens from 50 patients with lung adenocarcinoma were subjected to Sanger sequencing for 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. 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 (36.4% vs. 46.5%; P=0.019). Multivariate analysis revealed that exon 10 mutation was an independent prognostic factor (HR=3.787; P=0.033). 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 conclusion, mutation at exon 10 (c.763 C>T) occurs frequently and is an independent prognostic predictor in lung adenocarcinoma.
RBM10调节多种基因的表达,这些基因在男性肺腺癌中常发生突变。本研究证实了第10外显子突变与肺腺癌临床病理数据及预后的相关性。研究了该突变体对肺癌细胞生长和侵袭的调节作用。对50例肺腺癌患者的组织标本进行第10外显子突变的桑格测序。用携带野生型RBM10 cDNA或外显子突变cDNA的pcDNA3.1转染肺腺癌细胞,进行细胞活力、凋亡和侵袭实验。50例患者中有11例检测到第10外显子突变,在男性患者中频率较高[c.763 C>T,p.Arg241Cys为33.3%(10/30)],并且与美国癌症联合委员会分期(P=0.005)、淋巴结转移(P=0.019)显著相关,与野生型相比5年生存率较低(36.4%对46.5%;P=0.019)。多因素分析显示第10外显子突变是独立的预后因素(HR=3.787;P=0.033)。c.763 C>T的第10外显子突变显著促进肿瘤细胞增殖和侵袭能力,而野生型RBM10抑制肿瘤细胞侵袭。总之,第10外显子(c.763 C>T)突变在肺腺癌中频繁发生,是独立的预后预测指标。