Gong Wei-Jing, Yin Ji-Ye, Li Xiang-Ping, Fang Chao, Xiao Di, Zhang Wei, Zhou Hong-Hao, Li Xi, Liu Zhao-Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.
Tumour Biol. 2016 Jun;37(6):8349-58. doi: 10.1007/s13277-015-4497-5. Epub 2016 Jan 5.
Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.
长链非编码RNA（lncRNAs）在肿瘤发生和药物疗效中发挥着重要作用。铂类化疗是肺癌化疗的一线治疗方法。在本研究中，我们旨在探讨特征明确的肺癌lncRNA基因多态性与肺癌易感性及铂类化疗反应之间的关联。本研究共纳入498例肺癌患者和213例健康对照。其中，467例患者接受了至少两个周期的铂类化疗。采用等位基因特异性基质辅助激光解吸电离飞行时间质谱法对HOXA远端转录本反义RNA（HOTTIP）、HOX转录本反义基因间RNA（HOTAIR）、H19、CDKN2B反义RNA 1（ANRIL）、结肠癌相关转录本2（CCAT2）、转移相关肺腺癌转录本1（MALAT1）和母系表达基因3（MEG3）基因中的13个多态性进行基因分型。我们发现，携带HOTTIP rs5883064 C等位基因或rs1859168 A等位基因的患者患肺癌的风险增加（P分别为0.01、0.01）。CCAT2 rs6983267（P = 0.02，腺癌）和H19 rs2107425（P = 0.02，年龄小于50岁）与肺癌易感性密切相关。CCAT2 rs6983267、H19 rs2839698、MALAT1 rs619586和HOTAIR rs7958904在显性模型中与铂类化疗反应相关（P分别为0.02、0.04、P = 0.04、P = 0.01）。ANRIL rs10120688（P = 0.02，腺癌）和rs1333049（P = 0.04，小细胞肺癌）、H19 rs2107425（P = 0.02，小细胞肺癌）和HOTAIR rs1899663（P = 0.03，男性；P = 0.03，吸烟者）与铂类化疗反应相关。HOTTIP、CCAT2、H19、HOTAIR、MALATI、ANRIL基因多态性与肺癌易感性或铂类化疗反应显著相关。它们可能是预测肺癌风险和铂类化疗反应的潜在临床生物标志物。
