Author：Yanling Zhang, Dandan Ren, Beibei Mao, Xue Song, Wanning Yang, Henghui Zhang, Lisheng Cai

Background: As the fifth most common malignancies and the third leading cause of cancer death in the world, gastric cancer (GC) is often diagnosed in locally advanced or metastatic stage and, therefore, has a poor prognosis. Copy number instability (CNI) score, interpreted as the general measure of genomic instability, was reported as a prognosis predictor of some types of cancer, but its role in prognosis of GC patients remains unknown. The aim of the present study was to investigate its prognostic value in patients with GC after surgical resection and adjuvant chemotherapy. 

Methods: The present study included 120 patients who had received gastrectomy and adjuvant chemotherapy with stage II-IV GC. Follow-up was available for them. DNA was extracted from primary formalin-fixed paraffin-embedded (FFPE) tumor specimens and matched blood samples. Genomic profiles were analyzed by using a designed panel (1408 genes) based on next generation sequencing (NGS). 

Results: The most frequently mutated genes were TP53 (49%), PIK3CA (8%), RNF43 (6%) ERBB3 (6%) and APC (6%), and the most frequently amplified genes were TRPS1 (41%), COL1A2 (31%), CSMD3 (29%), ZFHX4 (29%), NAV3 (23%). CNI score was negatively correlated with OS, the CNI-high group had markedly shorter OS than CNI-low group (p= 0.0093). In addition, there were statistically significant differences in OS between different clinical staging (p= 0.0468). Moreover, the Cox proportional hazard model showed that CNI score was an independent prognosis factor in GC. 

Conclusions: The current study indicates that CNI score in primary tumor tissue is an independent predictive prognostic biomarker for GC.