Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer
Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer
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DOI：
10.2147/ott.s123685
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Wang, Dongjie
中科院分区：
文献类型：
--
作者：
Sang, Yulan;Bi, Xin;Wang, Dongjie
以前，已经在非小细胞肺癌（NSCLC）中鉴定了TGF β 1的几种多态性，并且已经证明变体C-509 T，T869 C和G915 C与较高的TGF-β 1循环水平相关。然而，对TGF-β 1多态性在癌症中的预后价值知之甚少。本研究通过对261例非小细胞肺癌患者的T869 C多态性进行基因分型，首次发现非小细胞肺癌患者，尤其是携带C等位基因的患者，血清TGF-β 1水平显著高于健康人。通过卡方检验和Fisher精确检验，我们发现TC/CC基因型与NSCLC患者的吸烟、临床TNM分期、淋巴结转移和远处转移呈正相关。Kaplan-Meier分析显示TT基因型患者的总生存率高于C等位基因携带者（TC + CC）。最后，多因素分析证实组织学、淋巴结转移和远处转移是NSCLC的独立预后因素，而T869 C多态性不是独立预后因素。综上所述，我们的数据，作为一个原则的证明，TGFB 1的T869 C多态性可能作为一个遗传修饰在NSCLC进展和一个有前途的预后标志物的生存NSCLC患者。
Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-beta 1. However, little is known about the prognostic value of TGF-beta 1 polymorphisms in cancers. In this study, by genotyping the TGF-beta 1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-beta 1 levels than healthy individuals. By using chi-square (chi(2)) test and Fisher's exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan-Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients.