Background Perioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients. Patients and methods We analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients. Results A risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17-0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21-0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17-0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17-0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23-0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02-0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies. Conclusion The identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.

中文翻译：

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一种新的基于治疗前基因表达的风险评分，可指导胃癌的治疗。

背景技术围手术期化疗是晚期胃癌患者的既定治疗方法。治疗选择基于临床分期（cT）。我们旨在建立和验证包括临床和分子因素在内的预后评分，以优化这些患者的治疗决策。患者和方法我们分析了来自两个学术中心的626例胃癌和胃食管连接癌，包括主要切除的患者和术前/术前治疗的患者。将患者分为训练组（N = 269）和验证组（N = 357）。通过定量PCR在切除的肿瘤中测量11个靶基因的表达。生成并验证了预测整体生存率（OS）的风险评分。通过分析10位患者的50个肿瘤区域来评估肿瘤内异质性。结果包括CCL5，CTNNB1，EXOSC3和LZTR1的表达以及临床参数cT，肿瘤定位和组织病理学类型在内的风险评分表明，两组OS的差异显着[危险比（HR）0.30; 95％置信区间（CI）0.17-0.52]。在独立队列（HR 0.32; 95％CI 0.21-0.51; P <0.001）以及主要切除的亚组（HR 0.30; 95％CI 0.17-0.54; P <0.001）和之前的人群中，风险评分已成功验证-/接受手术治疗的患者（HR 0.37； 95％CI 0.17-0.81； P = 0.009）。在主要切除的肠癌（HR 0.45； 95％CI 0.23-0.90； P = 0.020）和非肠道型癌（HR 0.1； 95％CI 0.02）中，高危和低危患者的OS也存在显着差异。 -0.42； P <0.001）。肿瘤内异质性分析表明，对于三个活检的假设分析，分类可靠性为95％。结论在围手术期化疗的背景下，确定的风险评分可大大有助于改善胃癌患者的管理。