Park Song Ee, Kim Hee Sung, Jung Eun-Jung, Suh Ja Hee, Min Hyeyoung, Chi Kyong-Choun, Kim Jong Won, Park Joong-Min, Hwang In Gyu
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea.
J Cancer. 2022 Jan 1;13(3):869-876. doi: 10.7150/jca.65145. eCollection 2022.
This study aimed to investigate the relationship between DNA damage response (DDR) related protein expression and clinical outcomes of patients with stage II and III gastric cancer undergoing gastrectomy. From January 2005 to December 2017, 217 gastrectomized patients with stage II and III gastric cancer were analyzed for disease-free and overall survival (DFS and OS, respectively) based on their DDR expression status. We performed the immunohistochemical assessment of MLH1, MSH2, at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded (FFPE) samples. : Among the 217 patients studied, the most common DDR gene whose expression was suppressed was high PARP-1 (n = 120, 55.3%), followed by ATM (n = 62, 28.6%), ARID1A (n = 45, 20.7%), MLH1 (n = 33, 15.2%), BRCA1 (n = 25, 11.5%), and MSH2 (n = 9, 4.1%). The low-expression PARP-1 group exhibited a significantly shorter 5-year OS rate than the high-expression PARP-1 group (48.1% vs. 62.7%; HR 1.519, 95% CI = 1.011-2.283, P = 0.044). In the multivariate OS analysis, TNM stage (II vs. III) (HR = 5.172, P < 0.001), low PARP-1 expression (HR = 1.697, P = 0.013) and adjuvant chemotherapy (HR = 0.382, P < 0.001) were the only significant prognostic factors. : Low PARP-1 expression level could be an indicator of poor prognosis in gastrectomized patients with stage II and III gastric cancer.
本研究旨在探讨DNA损伤反应(DDR)相关蛋白表达与接受胃切除术的II期和III期胃癌患者临床结局之间的关系。2005年1月至2017年12月,对217例行胃切除术的II期和III期胃癌患者,根据其DDR表达状态分析无病生存期和总生存期(分别为DFS和OS)。我们使用福尔马林固定石蜡包埋(FFPE)样本对错配修复蛋白同源物1(MLH1)、错配修复蛋白同源物2(MSH2)、富含AT交互结构域1(ARID1A)、聚腺苷二磷酸核糖聚合酶1(PARP-1)、乳腺癌易感基因1(BRCA1)和共济失调毛细血管扩张症突变基因(ATM)进行免疫组化评估。在217例研究患者中,表达受抑制最常见的DDR基因是高PARP-1(n = 120,55.3%),其次是ATM(n = 62,28.6%)、ARID1A(n = 45,20.7%)、MLH1(n = 33,15.2%)、BRCA1(n = 25,11.5%)和MSH2(n = 9,4.1%)。低表达PARP-1组的5年总生存率显著低于高表达PARP-1组(48.1%对62.7%;风险比1.519,95%置信区间= 1.011 - 2.283,P = 0.044)。在多因素总生存分析中,TNM分期(II期对III期)(风险比= 5.172,P < 0.001)、低PARP-1表达(风险比= 1.697,P = 0.013)和辅助化疗(风险比= 0.382,P < 0.001)是仅有的显著预后因素。低PARP-1表达水平可能是II期和III期胃癌胃切除患者预后不良的一个指标。