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叶酸代谢途径基因中的遗传变异可预测接受一线化疗的转移性结直肠癌患者的预后。

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy.

作者信息

Jiang Lu, Li Shuwei, Yuan Ming, Ma Ling, Lin Yu, Zhu Weiyou, Du Haina, Wang Meilin, Chen Tao, Zhu Lingjun

机构信息

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

Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.

出版信息

J Cancer. 2020 Sep 21;11(22):6507-6515. doi: 10.7150/jca.44580. eCollection 2020.

Abstract

The association between genetic variants in the folic acid metabolic pathway genes and survival, as well as the responses to chemotherapy of metastatic colorectal cancer (mCRC) patients has not been reported. The association between genetic variants in the folic acid metabolic pathway genes and progression-free survival (PFS) and overall survival (OS) of mCRC patients were analyzed using Cox regression model. The false discovery rate (FDR) correction method was conducted. The logistic regression model was used to explore the effects of the interested genetic variants on disease control rate (DCR). The Cancer Genome Atlas (TCGA) database was applied to compare gene expression differences. We found that rs3786362 G allele of thymidylate synthase () gene was significantly associated with PFS (P = 1.10 × 10), OS ( = 2.50 × 10) and DCR ( = 5.00 × 10). The expression of was overexpressed in CRC tissues compared with adjacent normal tissues. Furthermore, expression level decreased with respect to younger age and advanced tumor stage. Genetic variants in the folic acid metabolic pathway genes might serve as potential prognostic biomarkers for mCRC patients.

摘要

叶酸代谢途径基因中的遗传变异与转移性结直肠癌(mCRC)患者的生存以及化疗反应之间的关联尚未见报道。使用Cox回归模型分析叶酸代谢途径基因中的遗传变异与mCRC患者无进展生存期(PFS)和总生存期(OS)之间的关联。采用错误发现率(FDR)校正方法。使用逻辑回归模型探讨感兴趣的遗传变异对疾病控制率(DCR)的影响。应用癌症基因组图谱(TCGA)数据库比较基因表达差异。我们发现胸苷酸合成酶()基因的rs3786362 G等位基因与PFS(P = 1.10×10)、OS( = 2.50×10)和DCR( = 5.00×10)显著相关。与相邻正常组织相比,在结直肠癌组织中过表达。此外,表达水平随年龄较小和肿瘤分期进展而降低。叶酸代谢途径基因中的遗传变异可能作为mCRC患者潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0209/7545690/9788d1fcc442/jcav11p6507g001.jpg

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