Molecular characterization of colorectal adenoma and colorectal cancer via integrated genomic transcriptomic analysis

Abstract

IntroductionColorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain.MethodsIn this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data.ResultsDespite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice.ConclusionThis study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

“…MSI, on the other hand, is characterized by a high frequency of mutations in short repetitive DNA sequences, primarily due to defects in the DNA mismatch repair system. MSI-high tumors are more responsive to immunotherapies due to their increased mutational load. , …”