{"title":"Whole-Genome and RNA Sequencing Reveal Novel Insights into the Pathogenesis of Colorectal Cancer in Persons Living with HIV.","authors":"Yuxue Gao, Pengxiang Yang, Yuanyue Guan, Qiqi Ning, Jing Chang, Dexi Chen, Feili Wei, Yulin Zhang, Yuening Zhang","doi":"10.1089/aid.2025.0013","DOIUrl":null,"url":null,"abstract":"<p><p>In persons living with HIV (PWH), non-AIDS-related tumors, including colorectal cancer (CRC), have become major health concerns worldwide since the introduction of highly active antiretroviral therapy. To date, no study has addressed the underlying molecular mechanisms in PWH with CRC. To explore the impact of PWH with CRC, we sequenced total RNA and DNA from individuals with HIV-negative and PWH formalin-fixed paraffin-embedded (FFPE) CRC for transcriptome and genome analyses. We performed RNA and DNA extraction from FFPE samples, library preparation, total RNA sequencing, and whole-genome sequencing. A total of 1,705 genes were found to be differentially expressed genes (DEGs), including 1,121 upregulated DEGs and 584 downregulated DEGs, in PWH compared with HIV-negative CRC. Functional pathway analysis revealed that the DEGs were enriched mainly in infectious and immune diseases and various metabolic processes. The immune infiltration results revealed that the numbers of activated dendritic cells (aDCs), natural killer T cells (NKT cells), and T follicular helper cells (Tfh cells) were greater and that the number of memory B cells was lower in patients with CRC than in PWH. Twelve hub genes involved in interferon-stimulated genes (ISGs)-IFI44, MX1, OAS1, OAS3, BST2, IFIT1, FGF2, EGF, CCL3, CCL4, SHH, and PPARG-are positively related to aDC, NKT, Tfh, and memory B cells. We found highly analogous insertions, deletions, and functional annotations of the detected single nucleotide polymorphisms and indel mutations in PWH and patients with HIV-negative CRC. This study provides new insights into crucial ISGs, immune infiltration, immune variants, and pathways involved in CRC with HIV infection.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS research and human retroviruses","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/aid.2025.0013","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
In persons living with HIV (PWH), non-AIDS-related tumors, including colorectal cancer (CRC), have become major health concerns worldwide since the introduction of highly active antiretroviral therapy. To date, no study has addressed the underlying molecular mechanisms in PWH with CRC. To explore the impact of PWH with CRC, we sequenced total RNA and DNA from individuals with HIV-negative and PWH formalin-fixed paraffin-embedded (FFPE) CRC for transcriptome and genome analyses. We performed RNA and DNA extraction from FFPE samples, library preparation, total RNA sequencing, and whole-genome sequencing. A total of 1,705 genes were found to be differentially expressed genes (DEGs), including 1,121 upregulated DEGs and 584 downregulated DEGs, in PWH compared with HIV-negative CRC. Functional pathway analysis revealed that the DEGs were enriched mainly in infectious and immune diseases and various metabolic processes. The immune infiltration results revealed that the numbers of activated dendritic cells (aDCs), natural killer T cells (NKT cells), and T follicular helper cells (Tfh cells) were greater and that the number of memory B cells was lower in patients with CRC than in PWH. Twelve hub genes involved in interferon-stimulated genes (ISGs)-IFI44, MX1, OAS1, OAS3, BST2, IFIT1, FGF2, EGF, CCL3, CCL4, SHH, and PPARG-are positively related to aDC, NKT, Tfh, and memory B cells. We found highly analogous insertions, deletions, and functional annotations of the detected single nucleotide polymorphisms and indel mutations in PWH and patients with HIV-negative CRC. This study provides new insights into crucial ISGs, immune infiltration, immune variants, and pathways involved in CRC with HIV infection.
期刊介绍:
AIDS Research and Human Retroviruses was the very first AIDS publication in the field over 30 years ago, and today it is still the critical resource advancing research in retroviruses, including AIDS. The Journal provides the broadest coverage from molecular biology to clinical studies and outcomes research, focusing on developments in prevention science, novel therapeutics, and immune-restorative approaches. Cutting-edge papers on the latest progress and research advances through clinical trials and examination of targeted antiretroviral agents lead to improvements in translational medicine for optimal treatment outcomes.
AIDS Research and Human Retroviruses coverage includes:
HIV cure research
HIV prevention science
- Vaccine research
- Systemic and Topical PreP
Molecular and cell biology of HIV and SIV
Developments in HIV pathogenesis and comorbidities
Molecular biology, immunology, and epidemiology of HTLV
Pharmacology of HIV therapy
Social and behavioral science
Rapid publication of emerging sequence information.