Identification of Chondroitin Polymerizing Factor as a Biomarker for Colorectal Cancer by the Human Villi Development...

Emerging mounts of research support the ancestral theory of cancer, indicating that tumorigenesis and embryogenesis share many similar biological features, yet yield distinct outcomes. Gene co-expression networks underlie both embryonic development and tumorigenesis. We hypothesize that deviations in the gene interaction patterns in tumors compared to villi predispose to malignancy and worse prognosis.

By constructing a gene co-expression network of villi and colorectal cancer (CRC) and conducting functional enrichment analysis to identify "off-track genes." Cox regression assessed prognostic significance, while tissue microarrays evaluated protein expression and progression. Additionally, mRNA sequencing of chondroitin polymerizing factor (CHPF)-knockdown LOVO and SW480 cell lines was conducted and validated via in vitro assays.

We found that genes in villi and CRC have similar functions, but the genes that performed corresponding functions were not identical. Then, according to "off-track theory" and linear regression models, we obtained 24 genes whose aberrant expression was significantly associated with poor CRC survival. Notably, CHPF emerged as an adverse prognostic factor. Immunohistochemical analysis confirmed that CHPF is an independent prognostic marker for CRC. Furthermore, cell phenotype assays demonstrated that CHPF enhances proliferation and migration, suppresses apoptosis, and engages in the TNF signaling pathway.

These findings validate that villi development can serve as a research model for tumorigenesis, and identify CHPF is an independent oncogenic factor in CRC, suggesting its potential as a prognostic biomarker and a therapeutic target for clinical treatment.