長鏈非編碼核糖核酸MIR155HG其基因多型性與肺癌的相關性探討

肺癌主要分為小細胞肺癌 (Small cell lung cancer, SCLC) 與非小細胞肺癌 (Non-small cell lung cancer, NSCLC)，在NSCLC中有將近一半的比例是肺腺癌 (Lung adenocarcinoma, LUAD)。有些NSCLC患者的表皮生長因子受體 (Epidermal growth factor receptor, EGFR) 會在外顯子19發生剪接缺失突變 (In-frame deletion) 或是外顯子21 L858R發生點突變 (Point mutation)，而過往的研究發現EGFR發生突變的肺癌患者有較佳的預後。MIR155宿主基因 (MIR155HG) 是一種長鏈非編碼核醣核酸 (Long non-coding RNA, lncRNA) 並且在NSCLC被發現具有癌基因 (Oncogene) 的功能。本研究收集了271位肺腺癌患者並利用即時聚合酶連鎖反應 (Real-time polymerase chain reaction) 針對MIR155HG單核苷酸多型性(Single-nucleotide polymorphisms，SNPs) rs1893650、rs928883、rs767649以及rs414337與EGFR突變與否來探討其對於肺癌易感性之影響。我們的研究結果發現MIR155HG 的基因多型性在EGFR 野生型 (Wild type) 以及突變型(Mutation) 肺腺癌患者兩組之間並沒有呈現統計顯著差異。然而當我們進一步將這些肺腺癌患者的臨床病理特徵與MIR155HG的基因多型性進行分析之後，發現帶有MIR155HG rs1893650“TC + CC”基因多型性的EGFR 野生型肺腺癌患者有較大的風險進展成腫瘤細IV胞分化不良 (Poorly cell differentiation)，但是在EGFR 突變型的肺腺癌患者則沒有發現統計顯著差異。綜合上述，我們的研究結果發現帶有MIR155HG rs1893650“TC + CC”基因多型性的EGFR 野生型肺腺癌患者有較大的風險進展成腫瘤細胞分化不良。MIR155HG rs1893650的基因多型性或許可以做為預測肺腺癌病程進展與預後的生物標記 (Biomarker)。

Lung cancer was comprised with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About half of the NSCLC patients were individuals who with lung adenocarcinoma(LUAD). Some of the NSCLC patients may posses an in-frame deletion in exon 19 or L858R point mutation in exon 21 of the epidermal growth factor receptor(EGFR), and previous studies have associated the lung cancer patients who with EGFR mutation with better prognosis.MIR155 host gene (MIR155HG) is a long non-coding RNA(lncRNA),and was suggested as an oncogene in NSCLC. In this study, we analyzed four single-nucleotide polymorphisms (SNPs) of MIR155HGrs1893650, rs928883, rs767649, and rs4143370by real-time polymerase chain reaction to elucidate their effects on susceptibility between the EGFR wild-type and EGFR mutation LUAD patients.A total of 271 patients with LUAD were enrolled in our study, and each individual was classified into EGFR wild type or EGFR mutation. The results of our study have demonstrated that the genetic variants of MIR155HG polymorphisms showed no statistical significancebetween the EGFR wild type and EGFR mutation LUAD patients. However, after we further analyzed the clinicopathological charateristics the EGFR wild type LUAD patients who carried the MIR155HG rs1893650 “TC + CC” were found to be associated with greater risk to develop poorer cell differentiation. In contrast, no significant association was found between the EGFR mutation LUAD patients who carried the MIR155HG rs1893650 polymorphic variants.In conclusion, our results have demonstrated that the EGFR wild typeVILUAD patients who carried the MIR155HG rs1893650 “TC + CC”polymorphic variants were associated with greater risk to develop poorly cell differentiation. The MIR155HG rs1893650 gene polymorphisms may play a pivotal role as biomarker to predict LUAD cancer progression and prognosis.