Deciphering the proteomic landscape of pregnancy-associated colorectal cancer

The rising incidence of early-onset colorectal cancer (CRC) and delayed childbearing have led to increased pregnancy-associated CRC (PACRC), an exceedingly rare condition that remains biologically uncharacterized due to its scarcity. This study aimed to identify the unique biological features of PACRC, correlate them with clinical outcomes, and compare them to the genomic landscape of pregnancy-related breast cancer (PrBC).

We performed a mass spectrometry-based quantitative proteomic analysis of pathological CRC samples from PACRC patients and compared them with aged-matched non-pregnancy-associated CRC (NPACRC) patients. To investigate the broader effects of pregnancy on tumor biology and carcinogenesis, we analyzed gene expression data from PrBC samples and assessed the expression of pregnancy-associated pathways identified in PACRC within this context.

The colorectal cancer cohort included 8 PACRC and 12 NPACRC cases, with a median age of 31 years for PACRC and 33 years for NPACRC. Using the expression values of 2994 proteins, we identified multiple pathways with differential expression across conditions, particularly those linked to immune function. Functional enrichment analysis revealed PACRC exhibited enhanced immunity in the tumor microenvironment compared to NPACRC. This immune shift correlated with improved CRC survival in the TCGA dataset. Differential expression analysis of PrBC revealed that the immune pathways identified in PACRC were also altered in HER2 + PrBC, yet not in the other breast cancer subtypes. This underscores the differential regulation of pregnancy on tumorigenesis across cancer types.

Pregnancy associated may represent a distinct immune microenvironment subtype in which immune-related microenvironment may play a role in cancer pathogenesis.