# Complement and Coagulation Cascades Pathway was Inactivated in HIV-Associated Colorectal Cancer: Results from a Proteomics Study

## TL;DR

This study found that HIV-related colorectal cancer has unique proteomic changes, including reduced activity in a key immune pathway, which could help identify new biomarkers.

## Contribution

The study identifies HIV-specific proteomic alterations in colorectal cancer, particularly in the complement and coagulation cascades pathway.

## Key findings

- HIV-associated CRC shows distinct proteomic changes, including upregulated ribosome and downregulated complement and coagulation cascades pathways.
- Key proteins C8B and SERPINA1 in the complement and coagulation pathway are downregulated in HIV-related CRC.
- HIV infection increases the expression of upregulated DEPs but only slightly decreases downregulated ones compared to CPTAC data.

## Abstract

Background: Colorectal cancer (CRC) remains a leading cause of global cancer-related morbidity and mortality. Human Immunodeficiency Virus (HIV)-1 infection worsens colorectal cancer (CRC) outcomes.

Methods: To investigate mechanisms, we conducted Tandem Mass Tag proteomics on tumor (C) and adjacent normal tissues (A) from five HIV-positive (HIV+) and four HIV-negative (HIV-) CRC patients. Four comparisons were analyzed: HIV+C vs HIV+A (differentially expressed proteins, (DEPs)-1), HIV-C vs HIV-A (DEPs-2), HIV+A vs HIV-A (DEPs-3), HIV+C vs HIV-C (DEPs-4) (|fold change| ≥ 2, p < 0.05). The DEPs specifically affected by HIV (DEPs-5) underwent KEGG pathway enrichment analysis. The relative abundance of pathway-associated DEPs was compared with the data from CPTAC database. Key DEPs were validated by western blot/immunohistochemistry.

Results: We identified 749 (DEPs-1), 431 (DEPs-2), 4 (DEPs-3), and 21 (DEPs-4) DEPs. After excluding DEPs common to other comparisons, 592 HIV-specific DEPs (410 up-, 182 downregulated) were identified. KEGG enrichment revealed top altered pathways: upregulated ribosome (40 proteins) and downregulated complement and coagulation cascades (CCC pathway; 24 proteins). Comparison with the CPTAC database showed that HIV infection significantly increased the expression of upregulated DEPs but only slightly decreased the expression of downregulated ones. Downregulation of key CCC pathway proteins (C8B and SERPINA1) was confirmed by western blot and immunohistochemistry, respectively.

Conclusion: HIV-associated CRC exhibits distinct proteomic alterations, particularly ribosome and CCC pathway dysregulation. C8B and SERPINA1 are potential biomarkers for HIV-CRC.