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与接受卡培他滨辅助化疗的结直肠癌患者预后相关的Rs11479。

Rs11479 in Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

作者信息

Jia Xiongjie, Zhang Tao, Sun Junjie, Lin Hengxue, Bai Tianliang, Qiao Yating, Li Yaxin, Li Gang, Li Guicun, Peng Xinyu, Zhang Aimin

机构信息

Department of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2023 Mar 31;16:277-289. doi: 10.2147/PGPM.S397382. eCollection 2023.

Abstract

OBJECTIVE

gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy.

METHODS

A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of polymorphism and mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of according to genotype status was analyzed using non-parameter test.

RESULTS

Prevalence of rs11479 in among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, =0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of than that of patients with GG genotype (<0.001).

CONCLUSION

Polymorphism rs11479 in gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of . The conclusion of this study should be validated in prospective clinical trials subsequently.

摘要

目的

基因在结直肠癌(CRC)发生过程中具有潜在意义,且在卡培他滨代谢中发挥重要作用。本研究旨在确定基因多态性与接受以卡培他滨为基础的辅助化疗的CRC术后患者预后之间的关联。

方法

本研究回顾性纳入了218例接受手术切除及以卡培他滨为基础的辅助化疗的CRC患者。分别采集患者的外周血和外周血单个核细胞(PBMC)标本,用于基因多态性基因分型及mRNA表达检测。采用Kaplan-Meier生存分析对基因型与预后进行单因素分析,多因素分析采用Cox回归分析。根据基因型状态,采用非参数检验分析基因的mRNA表达。

结果

218例患者中基因rs11479的流行情况显示,rs11479的次要等位基因频率为0.20(GG型141例,GA型68例,AA型9例),符合Hardy-Weinberg平衡(P = 0.825)。关联分析表明,GG基因型和GA/AA基因型患者的无病生存期(DFS)中位数分别为3.1年和6.1年(P = 0.004)。此外,GG基因型和GA/AA基因型患者的总生存期中位数分别为5.0年和7.0年(P = 0.033)。多因素Cox回归分析显示,rs11479多态性是DFS的独立因素(HR = 1.64,P = 0.009)。另外,在65例PBMC标本中,mRNA表达结果表明,GA/AA基因型患者的基因mRNA表达显著高于GG基因型患者(P < 0.001)。

结论

基因中的rs11479多态性可能通过介导基因的mRNA表达来预测接受以卡培他滨为基础的辅助化疗的CRC患者的预后。本研究结论随后应在前瞻性临床试验中进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e06e/10072144/40bac78ec838/PGPM-16-277-g0001.jpg

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