Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity.
Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity.
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长非编码 RNA CASC8 rs10505477 多态性在肺癌易感性、铂类化疗反应和毒性中的临床意义
DOI：
10.3390/ijerph13060545
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发表时间：
2016-05-30
影响因子：
--
通讯作者：
Zhou HH
中科院分区：
文献类型：
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作者：
Hu L;Chen SH;Lv QL;Sun B;Qu Q;Qin CZ;Fan L;Guo Y;Cheng L;Zhou HH
长非编码RNA(Long Non-Coding RNA，LncRNA)CASC8rs10505477基因多态性与结直肠癌、胃癌、浸润性卵巢癌等多种癌症的发病风险相关，可能与胃癌患者术后接受铂类化疗的预后有关。到目前为止，还没有研究探讨LncRNA CASC8 rs10505477在肺癌易感性和治疗中的临床意义。在本研究中，我们对498例肺癌患者和213例健康对照进行了基因分型，以探讨rs10505477基因多态与中国人群肺癌风险的相关性。在498例患者中，467例用于化疗反应和毒性研究。在隐性模型中，单核苷酸多态(SNP)rs10505477与男性和腺癌亚组的肺癌危险性显著相关(校正OR=0.51，95%CI=0.29~0.90，p=0.02；校正OR=0.52，95%CI=0.30~0.89，p=0.02)。在优势模型中，其与铂类化疗反应密切相关(校正OR=1.58，95%CI=1.05~2.39，P=0.03)。此外，在显性模型(校正OR=0.59，95%CI=0.35~0.98，p=0.04)和加性模型(校正OR=0.62，95%CI=0.43~0.90，p=0.01)中，CASC8 rs10505477基因多态性与非小细胞肺癌(NSCLC)亚组的严重血液学毒性显著相关。此外，在优势模型中，rs10505477基因多态性与小细胞肺癌和顺铂亚组的胃肠道毒性显著相关(校正OR=7.82，95%CI=1.36~45.07，p=0.02；校正OR=1.94，95%CI=1.07~3.53，p=0.03)。因此，lncRNA CASC8 rs10505477可作为肺癌诊断的一个可能的危险标志物，并可用于预测肺癌患者铂类药物治疗的疗效和毒性。
Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.