Multigene mutation signatures in colorectal cancer patients: Predict for the diagnosis, pathological classification, staging and prognosis.

Abstract

e16113 Background: Like most cancers, early diagnosis of colorectal cancer (CRC) contributes to a good prognosis. Recently, some studies indicated that mutation gene signatures have good performances in predicting the treatment and prognosis in CRC patients. However, incomplete understanding of the genotype is not conducive to proper treatment. The objective was to give further genetic insights into CRC and provide more comprehensive references for clinical practice. Methods: In the training group, the whole genome sequencing (WGS), clinical, and demographic data of 531 patients were downloaded from The Cancer Genome Atlas (TCGA). The validation group contained 53 patients, which were collected in Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) from April 2014 to November 2018. The fresh tissues collected within 24 hours after operation were used to extract genomic DNA, and then sequenced with targeted next-generation sequencing (NGS) technology to examine somatic mutations and analyze relevant gene concerning clinical indicators. The correlation between gene variation distribution and various indexes such as cancer species, stage, total survival period, sex, age and race were evaluated. Results: A total of 44 mutant genes with mutation frequencies above 5% were found in both TCGA cases and validated cases. Mutations of TP53, APC, KRAS, BRAF and ATM covered 97.55% of TCGA population and 83.02% validation patients, which were proved to be associated with the development of CRC and could be used as a diagnostic signature. Importantly, mutations of TP53, PIK3CA, FAT4, FMN2 and TRRAP had a remarkable difference between early (I/II) and advanced (III/IV) stage patients (P < 0.0001). Besides, we also confirmed that PIK3CA, LRP1B, FAT4 and ROS1 were a mutated gene signature for the prognosis, LRP1B portended to a higher of recurrence and shorter progression-free survival (PFS); mutation of FAT4 portended to a lower of recurrence and longer PFS, which could predict the recurrence and survival of CRC patients. Conclusions: We have indicated gene mutation signatures related to the diagnosis, pathological classification, staging and prognosis in CRC, which provides further insights into the study of CRC genotype. It is helpful to further improve the personalized diagnosis and treatment.