UGT1A1基因多态性及ERCC1、BRCA1、TYMS、RRM1、TUBB3、STMN1和TOP2A在胃癌中的表达的临床意义
Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer.
作者信息
Cao Yongkuan, Zhang Guohu, Wang Peihong, Zhou Jun, Gan Wei, Song Yaning, Huang Ling, Zhang Ya, Luo Guode, Gong Jiaqing, Zhang Lin
机构信息
Department of Gastrointestinal Surgery, Center of General Surgery of P.L.A., Chengdu Army General Hospital, No.270 Rongdu avenue, Chengdu, 610083, Sichuan Province, China.
出版信息
BMC Gastroenterol. 2017 Jan 5;17(1):2. doi: 10.1186/s12876-016-0561-x.
BACKGROUND
Individualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed.
METHODS
Ninety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated.
RESULTS
The expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at -211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or -3156 of UGT1A1 tended to have a local invasion.
CONCLUSIONS
The UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance.
背景
个体化治疗方案是近年来针对疾病的一种备受关注的方法，其中寻找生物标志物被认为是首要且最重要的。因此，本研究的目的是调查UGT1A1、ERCC1、BRCA1、TYMS、RRM1、TUBB3、STMN1和TOP2A基因是否为胃癌的潜在生物标志物，据我们所知，尚未有相关研究。
方法
收集了2012年5月至2015年3月期间胃癌患者的98份组织标本。采用多重分支DNA液相芯片技术检测ERCC1、BRCA1、TYMS、RRM1、TUBB3、STMN1和TOP2A的mRNA表达。通过直接测序确定UGT1A1基因多态性。此外，研究了基因表达、多态性与临床病理特征之间的相关性。
结果
TYMS、TUBB3和STMN1的表达与胃癌患者的年龄、性别和家族史等临床病理特征显著相关，但与胃癌患者的分化程度、生长方式、转移和TNM分期无关。没有临床特征与ERCC1、BRCA1、RRM1和TOP2A的表达相关。此外，UGT1A1基因-211位点携带G等位基因的患者易患管状腺癌，而UGT1A1基因*28位点携带6TAA或-3156位点携带G等位基因的个体往往有局部侵袭。
结论
UGT1A1基因多态性可能有助于筛查胃癌的高危人群，而TYMS、TUBB3和STMN1可能是预后和化疗指导的潜在生物标志物。
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