Whole-Genome and RNA Sequencing Reveal Novel Insights into the Pathogenesis of Colorectal Cancer in Persons Living with HIV.

IF 1.5 4区 医学 Q4 IMMUNOLOGY
Yuxue Gao, Pengxiang Yang, Yuanyue Guan, Qiqi Ning, Jing Chang, Dexi Chen, Feili Wei, Yulin Zhang, Yuening Zhang
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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.

全基因组和RNA测序揭示了HIV感染者结直肠癌发病机制的新见解。
在艾滋病毒感染者(PWH)中,自采用高效抗逆转录病毒疗法以来,非艾滋病相关肿瘤,包括结直肠癌(CRC),已成为全世界主要的健康问题。到目前为止,还没有研究解决PWH合并CRC的潜在分子机制。为了探索PWH对CRC的影响,我们对hiv阴性和PWH福尔马林固定石蜡包埋(FFPE) CRC患者的总RNA和DNA进行了测序,用于转录组和基因组分析。我们对FFPE样品进行了RNA和DNA提取、文库制备、总RNA测序和全基因组测序。与hiv阴性CRC相比,PWH中共有1705个基因存在差异表达基因(deg),包括1121个表达上调的deg和584个表达下调的deg。功能通路分析显示,DEGs主要富集于感染性和免疫性疾病以及各种代谢过程中。免疫浸润结果显示,CRC患者的活化树突状细胞(adc)、自然杀伤T细胞(NKT细胞)和T滤泡辅助细胞(Tfh细胞)数量高于PWH,记忆B细胞数量低于PWH。12个参与干扰素刺激基因(ISGs)的枢纽基因ifi44、MX1、OAS1、OAS3、BST2、IFIT1、FGF2、EGF、CCL3、CCL4、SHH和ppar与aDC、NKT、Tfh和记忆B细胞呈正相关。我们在PWH和hiv阴性CRC患者中发现了高度相似的插入、缺失和检测到的单核苷酸多态性和indel突变的功能注释。这项研究为CRC合并HIV感染的关键isg、免疫浸润、免疫变异和途径提供了新的见解。
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来源期刊
CiteScore
3.10
自引率
6.70%
发文量
201
审稿时长
3-6 weeks
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.
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