Transcriptomics

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Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions


ABSTRACT: Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy that is linked to high-risk Human papillomavirus (HPV) infection. It is often preceded by precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). The incidence of ASCC varies across populations, with heightened risk in HIV-positive individuals. In a previous study, we characterized the anal microbiome in high-risk HIV-exposed MSM and TGW subjects. We revealed oncogenic viromes and pertinent bacterial species associated with anal SILs. Our current investigation aimed to delineate transcriptomic and metatranscriptomic changes during the progression from precancerous lesions to ASCC. We collected 70 anal tissue samples across various lesion stages (LGSIL, HGSIL, and ASCC). Our metatranscriptomic analysis revealed that Fusobacterium nucleatum, F. gonidiaformans, Bacteroides fragilis, Campylobacter ureolyticus, and Cribacterium bergeronii were more prevalent in ASCC than in precancerous lesions. These bacterial species contributed with gene encoding enzymes (e.g.: Acca, glyQ, eno, pgk and por) and oncoproteins (FadA and dnaK) revealing potential new markers for diagnosis or treatment approaches. Our unsupervised transcriptome analysis identified two distinct sample clusters based on histological diagnosis, immune infiltrate, HIV and HPV status, and pathway activities such as immune activation, cell cycle, and antiviral signaling that recapitulate the natural history of anal cancer progression. Mutations were observed affecting KMT2C (30%), PIK3CA (21%), EP300 (21%) and NOTCH1 (13%) cancer driver genes among ASCC but also in precancerous lesions. Our study provides insights into the molecular mechanisms governing anal cancer progression, offering valuable information that may help to stratify HGSIL cases with low- or high-risk progression to the malignant stages.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253560 | GEO | 2024/08/04

REPOSITORIES: GEO

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