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转录因子多态性对中国肝细胞癌患者的预后影响。

The prognostic impacts of transcription factor polymorphisms in Chinese hepatocellular carcinoma patients.

作者信息

Xia Haiyan, Wen Juan, Zhao Weiyong, Gu Dongying, Hu Zhibin, Chen Jinfei, Xu Zhi

机构信息

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.

出版信息

Oncotarget. 2017 Jul 17;8(41):69823-69832. doi: 10.18632/oncotarget.19310. eCollection 2017 Sep 19.

Abstract

TEA domain (TEAD) transcription factors play an important role in hepatocellular carcinoma (HCC) development and progression by regulating the expression of a number of genes. However, the association of their genetic variations with HCC prognosis remains elusive. Seven potentially functional single nucleotide polymorphisms in - (rs2304733, rs10831923, rs12104362, rs3745305, rs11756089, rs2076173, rs7135838) were genotyped from 331 hepatitis B virus positive HCC patients using the Sequenom MassARRAY iPLEX platform. The rs2076173 C allele and rs11756089 T allele were identified as protective alleles as they were significantly associated with longer median overall survival time (MST). The T allele of rs2076173 was significantly associated with HCC survival independent of age, gender, smoking and drinking status, BCLC stage, and chemotherapy or TACE status (HR = 0.73, 95% CI = 0.56-0.93, = 0.012). This protective effect was more prominent for patients who were non-drinkers ( for multiplicative interaction = 0.002). Patients had more than one of these protective alleles had significant longer MST of 19.25 months than those had none (MST=12.85 months, adjusted HR = 0.56, 95% CI = 0.33-0.95, =0.030), especially for those non-drinkers (adjusted HR = 0.48, 95% CI = 0.32-0.74, = 0.001). These findings suggested that rs2076173 and rs11756089 in gene could serve as genetic markers for favorable survival in the Chinese HCC patients.

摘要

TEA 结构域(TEAD)转录因子通过调控多个基因的表达,在肝细胞癌(HCC)的发生和发展中发挥重要作用。然而,其基因变异与 HCC 预后的关联仍不清楚。利用 Sequenom MassARRAY iPLEX 平台,对 331 例乙型肝炎病毒阳性 HCC 患者的 7 个潜在功能性单核苷酸多态性(rs2304733、rs10831923、rs12104362、rs3745305、rs11756089、rs2076173、rs7135838)进行基因分型。rs2076173 的 C 等位基因和 rs11756089 的 T 等位基因被确定为保护性等位基因,因为它们与更长的中位总生存时间(MST)显著相关。rs2076173 的 T 等位基因与 HCC 生存显著相关,独立于年龄、性别、吸烟和饮酒状况、BCLC 分期以及化疗或 TACE 状况(HR = 0.73,95%CI = 0.56 - 0.93,P = 0.012)。对于不饮酒的患者,这种保护作用更为显著(相乘交互作用 P = 0.002)。具有一个以上这些保护性等位基因的患者的 MST 显著长于没有这些等位基因的患者,为 19.25 个月(MST = 12.85 个月,调整后 HR = 0.56,95%CI = 0.33 - 0.95,P = 0.03),尤其是不饮酒的患者(调整后 HR = 0.48,95%CI = 0.32 - 0.74,P = 0.001)。这些发现表明,基因中的 rs2076173 和 rs11756089 可作为中国 HCC 患者良好生存的遗传标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fdb/5642519/745f5ba17801/oncotarget-08-69823-g001.jpg

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