A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer. (23rd October 2017)

• Record Type: Journal Article
• Authors: Bauer, L; Hapfelmeier, A; Blank, S; Reiche, M; Slotta-Huspenina, J; Jesinghaus, M; Novotny, A; Schmidt, T; Grosser, B; Kohlruss, M; Weichert, W; Ott, K; Keller, G
• Is Part Of: Annals of oncology. Volume 29:Number 1(2018)
• Page Start: 127
• Page End: 132
• Publication Date: 2017-10-23
• Subjects: gastric carcinoma -- prognosis -- risk score -- perioperative chemotherapy -- gene expression; Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdx685
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: 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.