背景:迄今为止,缺失错配修复(dMMR)的作用在胃癌中仍有待证实,很难判断其临床应用价值。我们的研究旨在探讨MMR状态如何影响胃切除术患者的预后,以及dMMR胃癌患者新辅助化疗和辅助化疗的疗效。
方法:包括来自中国4家高容量医院的具有一定的dMMR病理诊断或免疫组织化学熟练MMR(pMMR)的胃癌患者。倾向评分匹配用于以1:2的比率匹配具有dMMR或pMMR的患者。使用Kaplan-Meier方法绘制总生存期(OS)和无进展生存期(PFS)曲线,并使用对数秩检验进行统计学比较。使用基于风险比(HR)和95%置信区间(CI)的单变量和多变量Cox比例风险模型来确定生存的风险因素。
结果:总计,对6176例胃癌患者的数据进行了最终分析,在293例患者中观察到一种或多种MMR蛋白的表达缺失(293/6176,4.74%)。与pMMR患者相比,dMMR患者年龄较大(≥66,45.70%vs.27.94%,P<.001),远端位置(83.51%vs.64.19%,P<.001),肠型(42.21%vs.34.46%,P<.001),在较早的pTNM阶段(pTNMI,32.79%与29.09%,P=.009)。在PSM之前,dMMR胃癌患者的OS优于pMMR患者(P=0.002);然而,PSM后dMMR患者未观察到这种生存优势(P=.467).至于围手术期化疗,多变量Cox回归分析结果显示,围手术期化疗不是影响胃癌患者PFS和OS的独立预后因素(HR=0.558,95%CI,0.270-1.152,P=.186,HR=0.912,95%CI,0.464-1.793,P=.822)。
结论:结论:围手术期化疗不能延长dMMR胃癌患者的OS和PFS。
To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our
study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer.
Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival.
In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively).
In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.