Copy Number Alterations Predict the Survival of Early Colorectal Cancer with Depressed Morphology

Background: Depressed colorectal neoplasms exhibit a high malignant potential and may become invasive rapidly but their genomic alterations remain unknown. We investigated the genomic alterations of depressed neoplasms and potential implications on long-term survival. Methods: We examined 20 depressed neoplasms and 15 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations in an independent sample of 37 depressed and 42 polypoid neoplasms. Specific copy number alterations were tested in 530 colorectal cancers in order to clarify the clinical outcome of depressed colorectal neoplasms. Findings: Copy number alterations in MYC, CCNA1, and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. In the validation set, the panel presented a positive predictive value, sensitivity and accuracy of 80·0%, 75·7% and 79·7% respectively for discriminating the depressed neoplasms. colorectal cancers developing from depressed neoplasms account for 22·1% of all colorectal cancers and have a significantly more unfavorable progression-free survival compared with colorectal cancer without those biomarkers, especially in stage I, T1+2, and proximal cancers. Interpretation: In this article, we characterize the genome-wide landscape in the depressed neoplasm and its specific biosignature. The D-marker panel may help to optimize the treatment of depressed neoplasms and surveillance strategies, and develop more effective molecular screening tests in the future. Funding Statement: Funding by the National Taiwan University Hospital (Grand Number: NTUH 107-M3990, NTUH 108-M4209), Ministry of Science and Technology, Taiwan (Grant Number: MOST-105-2314-B-002-047, MOST106-2319-B-002-002, MOST107-2319-B-002-002), and as well as the “Center of Precision Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.Declaration of Interests: The authors declare that they have no conflicts of interest.Ethics Approval Statement: Before initiation, this study received approval (No. 201712033RINC) from the Institutional Review Board and Ethical Committee of National Taiwan University Hospital.