Work

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

Year: 2026

Type: article

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.

Source: Journal of Cancer

DOI: 10.7150/jca.124804

Authors: Shixian Lian, Lei Li, Yuexiang Yang, Siyuan Liu, Shu Song, Lijun Zhang

Institutions: Fudan University, Shanghai Public Health Clinical Center, Shanghai Jiao Tong University, Shanghai Ninth People's Hospital

Language: English

Topic: Viral-associated cancers and disorders

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337