Genetic or non-genetic prognostic factors in colon cancer

Abstract

Colorectal cancer (CRC) is one of the major contributors to cancer-related deaths worldwide. Patient classification at the time of diagnosis is a key factor that defines prognosis and is a critical element in determining appropriate treatment. Many researches were made on classifying patients by prognostic factors or gene expression profiles (GEPs). This study was trying to identify whether a prognostic factor was genetic or not by using GEPs. The number of differentially expressed genes (DEGs) was used as a statistic to test whether the GEPs were different for patient groups of two factor-statuses. Random permutation re-sampling was utilized for evaluating the significance of GEP difference. If significant GEP difference were observed, the factor would be considered as genetic. If GEP difference were largely less significant than the difference of relapse-free survival (RFS) rates, the RFS rate difference might not be owed to the gene set, the factor would be considered as non-genetic, or partly non-genetic. Non-genetic factors should be taken into account to complement the future gene expression classifiers. An application was made on public dataset GSE40967, which contains GEP data of 566 colon cancer patients, messages of tumor-node-metastasis (TNM) stages, biomarker (DNA mismatch repair [MMR], CpG island methylator phenotype [CIMP], chromosomal instability [CIN], KRAS, BRAF, TP53, sex, location) statuses, age at diagnosis, chemotherapy statuses, and relapse-free survival (RFS) messages. It was observed that there were significant GEP differences and significant RFS rate differences among the stages of T, N, and M. So T, N, and M stages might be genetic and prognostic. The RFS rate difference was much significant than the GEP difference between some statuses of M, N, or T. Factor M, N, and T might be partly nongenetic. MMR might be genetic and prognostic due to both the GEP difference and RFS rate difference were significant. Significant GEP differences were observed for CIMP, CIN, KRAS, BRAF, TP53, sex, location, and age. These factors might be genetic. But their RFS rate differences were not significant.