Analysis of multi-omics differences in left-side and right-side colon cancer

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Colon cancer is a prevalent digestive tract malignancy.
• Left-side colon cancer (LCC) and right-side colon cancer (RCC) display differing prognoses, outcomes, and chemotherapy responses.
• Understanding these anatomic subtypes is crucial for effective colon cancer management.

Purpose of the Study:

• To investigate the clinical, transcriptomic, and mutation differences between LCC and RCC.
• To identify distinct molecular mechanisms driving LCC and RCC.
• To develop prognostic signatures for individualized risk assessment in colon cancer patients.

Main Methods:

• Utilized transcriptome, clinical, and somatic mutation data from TCGA for 390 colon cancer patients (172 LCC, 218 RCC).
• Performed multi-omics analysis comparing clinical characteristics, immune microenvironment, gene expression, and mutation profiles of LCC and RCC.
• Validated prognostic signatures using internal and external datasets (GSE39582).

Main Results:

• RCC demonstrated a significantly worse prognosis and higher immune infiltration compared to LCC.
• Identified 360 differentially expressed genes between LCC and RCC.
• Revealed distinct dominant mutations: BRAF/KRAS in RCC (mutually exclusive with APC) and APC in LCC, indicating different molecular drivers.
• Developed 4-mRNA (LCC) and 6-mRNA (RCC) signatures with high predictive accuracy as independent prognostic factors.

Conclusions:

• Anatomic subtyping of colon cancer is vital for early diagnosis and prognostic risk stratification.
• The identified molecular differences and prognostic signatures offer insights for personalized treatment strategies for LCC and RCC.
• This research supports tailored therapeutic approaches based on colon cancer laterality.