Define a good prognosis of codon 659-mutated and concomitant genomic signatures in CRC: an analysis of the cBioPortal database.

BACKGROUND

Heterogeneity of colorectal cancer (CRC) leads to significant differences in Overall Survival (OS). is a new predictive marker for prognosis and anti-/ combinatory therapies of CRC recently. However, few studies focused on the relationship between and co-mutation characteristics and prognosis. This study aims to explore the different prognostic subtypes of -mutated CRC by analyzing the association of clinicopathological and genomic characteristics with survival outcomes.

METHODS

The clinical characteristics, mutational characteristics, and survival data of CRC patients were obtained for -mutated analysis from cBioPortal. All mutation data were filtered by the 1021-panel (Geneplus-Beijing, China), and the processed data were used to analyze the predictive value of -mutated to OS and concomitant co-mutations. Cox regression analysis was selected to explore prognostic biomarkers, and finally, and MSI were selected for subgroup analysis. The independent validation cohort comprised 339 cases of stage IV CRC from Beijing Hospital.

RESULTS

11 datasets with 4028 patient data were screened for this study. The most common variant was frameshift, which occurred in codon 659-mutated of exon 9, including p.G659Vfs41 (N=116) and p.G659Sfs87 (N=2). codon 659-mutated occurred frequently in right-sided CRC (59.32%, N=70, P<0.0001), and rarely in the left-sided (11.02%, N=13). The incidence of TMB-H in the codon 659-mutated group was 93.22% (110/118), and MSI-H was 78.81% (93/118). Univariate Cox analysis and multivariate Cox analysis showed that MSI-H was the most significantly different biomarker for better prognosis (P=0.004, HR=3, CI 1.4-6.4), and Class 1 V600E was the most different biomarker for worse prognosis (P<0.001, HR=0.3, CI 0.21-0.42). codon 659-mutated with non-class 1 -mutated or MSI-H suggests a better prognosis in CRC. We found that G1 ( codon 659-mutated, non-class 1 -mutated, and MSl-H) had a better PFS and OS. The mutation difference analysis showed that the core genes related to the cancer signaling pathway (PI3K-Akt signaling pathway, MicroRNAs pathway, DNA damage repair, and tumor suppressor genes) were highly frequent in G1. The analysis comparing the core gene mutation difference between -mutated and wild-type in the validation cohort yielded consistent conclusions.

CONCLUSIONS

In CRC, we found that the G1 cohort had the best prognosis, and patients with Non-codon 659-mutated, V600E and MSS had the worst prognosis. This may provide clinical value for patients' further accurate prognosis prediction, curative effect prediction, and follow-up management of patients.