Impact of a haplotype (composed of the APC, KRAS, and TP53 genes) on colorectal adenocarcinoma differentiation and patient prognosis.

BACKGROUND

Many types of gene mutation are associated with the drug resistance of cancer cells. XELOX is a new and efficient surgical adjuvant chemotherapy for colorectal adenocarcinoma. However, drug-resistant related genetic mutations associated with this treatment remain unknown.

METHODS

Next-generation sequencing (NGS) was performed on 36 colorectal cancer patients to identify mutations among patients with residual tumors following preoperative chemotherapy. Enrichment and prognosis of these mutations were evaluated in a TCGA cohort. The pathology of cases with poor prognosis-related mutations was also determined.

RESULTS

A sequence of SNPs associated with the APC, KRAS, and TP53 genes in 13 of 19 subjects with residual tumors after preoperative chemotherapy was identified. Using survival analysis data from 317 cases in the TCGA database, a prognosis-related haplotype composed of SNPs from APC, KRAS, and TP53 was assembled. Colorectal cancer patients with these mutations had a lower 5-year tumor-specific survival rate than those without (p < 0.05). Most patients with these mutations were at a higher clinical stage (III-IV) of disease. Enrolled subjects with the identified haplotype tended to have poor cancer cell differentiation.

CONCLUSIONS

The prognosis-related haplotype can be used as a marker of drug resistance and prognosis in colorectal cancer patients after preoperative chemotherapy.