Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response
Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response
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DOI：
10.1007/s13277-015-4497-5
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Liu, Zhao-Qian
中科院分区：
文献类型：
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作者：
Gong, Wei-Jing;Yin, Ji-Ye;Liu, Zhao-Qian
长链非编码RNA（lncRNA）在肿瘤发生和药物疗效中起重要作用。以铂类为基础的化疗是肺癌化疗的一线治疗方法。本研究旨在探讨肺癌lncRNA基因多态性与肺癌易感性和铂类药物化疗反应的关系。研究共招募了498名肺癌患者和213名健康对照。其中，467例患者接受了至少两个周期的铂类化疗。通过等位基因特异性MALDI-TOF质谱法对HOXA远端转录物反义RNA（HOTTIP）、HOX转录物反义基因间RNA（HOTAIR）、H19、CDKN 2B反义RNA 1（ANRIL）、结肠癌相关转录物2（CCAT 2）、转移相关肺腺癌转录物1（MALAT 1）和母体表达基因3（MEG 3）基因的13个多态性进行基因分型。我们发现HOTTIP rs 5883064 C等位基因或rs 1859168 A等位基因的患者患肺癌的风险增加（分别为P = 0.01，P = 0.01）。CCAT 2 rs6983267（P = 0.02，腺癌）和H19 rs 2107425（P = 0.02，年龄<50岁）与肺癌易感性有较强的相关性。在显性模型中，CCAT 2 rs6983267、H19 rs 2839698、MALAT 1 rs619586和HOTAIR rs7958904与含铂化疗反应相关（分别为P = 0.02、P = 0.04、P = 0.04、P = 0.01）。ANRIL rs 10120688（P = 0.02，腺癌）和rs 1333049（P = 0.04，小细胞肺癌），H19 rs 2107425（P = 0.02，小细胞肺癌）和HOTAIR rs 1899663（P = 0.03，男性; P = 0.03，吸烟者）与铂类化疗的反应相关。HOTTIP、CCAT 2、H19、HOTAIR、MALATI、ANRIL基因多态性与肺癌易感性或含铂化疗疗效显著相关。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。
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.