Han Rongbo, Wei Jingsun, Zhang Honghong, Su Xinyu, Chu Xia, Chen Yuetong, Gong Yang, Wang Xiujuan, Shi Junfeng, Chen Jinfei
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Department of Oncology, Taixing People's Hospital, Taixing, Jiangsu,People's Republic of China.
Cancer Manag Res. 2018 Jun 6;10:1429-1437. doi: 10.2147/CMAR.S158647. eCollection 2018.
This study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC).
Samples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy.
TS (rs34743033) variant genotypes significantly prolonged the median overall survival (OS) time compared to the patients who only received adjuvant chemotherapy (HR 1.604, 95% CI 1.068-2.410, =0.021). Moreover, 3R/3R variant genotypes were demonstrated to have a positive effect on the OS of patients who received chemotherapy based on cisplatin (HR 1.754, 95% CI 1.041-2.954, =0.031) compared to oxaliplatin. A stratification analysis indicated that 2R/3R and 2R/2R variant genotypes were associated with inferior survival in GC patients with intestinal-type tumors, tumor less than 5 cm in size, and poorly differentiated tumors (<0.05). However, RUNX1 (rs2014300) AA genotypes markedly increased the risk of death in GC patients compared with the GG/GA genotypes (=0.007), but no significant difference was observed between chemotherapy based on platinum. The stratification analysis showed that the GA/AA genotype was significantly associated with inferior survival in well to moderately differentiated tumors (HR 2.001, 95% CI 1.082-3.703, =0.023).
These preliminary results indicated that the two polymorphisms had a significant effect on postoperative adjuvant chemotherapy. TS (rs34743033) and RUNX1 (rs2014300) may be used as biomarkers to predict prognosis and select chemotherapy regimens in GC patients.
本研究旨在探讨II期和III期胃癌（GC）患者胸苷酸合成酶（TS）和 runt相关转录因子1（RUNX1）单核苷酸多态性的临床相关性。
收集661例II期和III期胃癌术后患者的样本。对261例接受术后基础铂类和氟尿嘧啶化疗方案的患者以及400例未接受化疗的患者进行TS（rs34743033）和RUNX1（rs2014300）基因分型。
与仅接受辅助化疗的患者相比，TS（rs34743033）变异基因型显著延长了中位总生存期（OS）（风险比[HR]1.604，95%置信区间[CI]1.068 - 2.410，P = 0.021）。此外，与奥沙利铂相比，3R/3R变异基因型对接受顺铂化疗患者的总生存期有积极影响（HR 1.754，95% CI 1.041 - 2.954，P = 0.031）。分层分析表明，2R/3R和2R/2R变异基因型与肠型肿瘤、肿瘤大小小于5 cm且分化差的GC患者生存期较差相关（P < 0.05）。然而，与GG/GA基因型相比，RUNX1（rs2014300）AA基因型显著增加了GC患者的死亡风险（P = 0.007），但基于铂类的化疗之间未观察到显著差异。分层分析显示，GA/AA基因型与高分化至中分化肿瘤患者生存期较差显著相关（HR 2.001，95% CI 1.082 - 3.703，P = 0.023）。
这些初步结果表明，这两种多态性对术后辅助化疗有显著影响。TS（rs34743033）和RUNX1（rs2014300）可作为预测GC患者预后和选择化疗方案的生物标志物。
