Abstract
e15098 Background: The incidence and mortality of cancer have been increasing in China, of which colorectal cancer (CRC) is ranking the fifth and among the leading cause of cancer-related deaths .Prognostic biomarker for colon cancer treated with standard adjuvant chemotherapy was rare and inconsistent, as gene mutations accumulation contribute to the carcinogenesis, available biomarkers may emerge by genome investigation. Methods: Whole exome sequencing was performed in 13 stage III colon cancers to identify gene alternations in patients with different outcomes, followed by 350 stage II-III colon cancers samples, of which clinicopathological characteristics and survival information were collected simultaneously to evaluate the clinical relevance in this cohort for evaluation of novel gene biomarkers. Results: Eight genes (CD97, ZNF568, WARS2, IL6R, APPL2, C9orf117, ANKRD32, ZNF443) were identified as differently expressed between two groups of good (DFS > 60 months) and poor (DFS < 25 month) separated according to treatment outcomes. ZNF443 was detected in 81.7% (286/350) samples, and ZNF443 (CA) was more common in male compared with female (56.0% vs 40.8%, P = 0.011).ZNF443 (CA) distribution differed related to different N stage, only stage N0 shared a higher frequency over 50% (P = 0.026).ANKRD32 was detected in 212 (93.8%) tumors, and ANKRD32 (CA) appeared more in left sites (included left colon and sigmoid colon, 61.1% vs 41.9%, P = 0.006). Moreover, ANKRD32 (CA) was significantly associated with superior disease-free survival (DFS) in stage III colon cancer patients (P = 0.044, HR 0.49, 95% CI0.24-0.98).Tumor nodal stage appeared as independent prognostic factor for DFS and over-all survival (OS) in stage II-III colon cancer (P < 0.05), and low tumor differentiation indicated a worse OS for colon cancers. While no other significant association was obtained between genes and survival in present study. Conclusions: Whole exome sequencing was efficient in discovering novel gene biomarkers in clinical evaluation. ANKRD32 was independently prognostic for DFS in stage III colon cancer.
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