Ontology highlight
ABSTRACT:
PROVIDER: PRJNA832742 | ENA |
REPOSITORIES: ENA
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Project description: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.
2024-08-04 | GSE253560 | GEO
Project description:Etiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCC) respond well to chemoradiotherapy, for undetermined reasons, a subgroup of patients experience a poor outcome. Despite cumulative efforts for discovering independent predictors for overall survival, both nodal status and tumor size are still the only reliable factors predicting patient outcome. In the present study, we correlated both proteomic signatures and clinicopathological features of neoplastic lesions arising from two distinct portions of the anal canal: the lower part (squamous zone) and the more proximal anal transitional zone. Although microdissected cancer cells appeared indistinguishable by morphology (squamous phenotype), unsupervised clustering analysis of the whole proteome significantly highlighted the heterogeneity that exists within anal canal tumors. More importantly, two region-specific subtypes of SCC were revealed. The expression profile (sensitivity/specificity) of several selected biomarkers (keratin filaments) further confirmed the subclassification of anal (pre)cancers based on their cellular origin. Less commonly detected compared to their counterparts located in the squamous mucosa, SCC originating in the transitional zone displayed more frequently a poor or basaloid differentiation and were significantly correlated with reduced disease-free and overall survivals. Taken together, we present for the first time direct evidence that anal canal SCC comprises two distinct entities with different cells of origin, proteomic signatures and survival rates. This study forms the basis for a novel dualistic classification of anal carcinoma with implications for management, outcome expectations and possibly therapeutic approaches.
2016-12-20 | PXD004859 | Pride
Project description:Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. Specimens from 46 rectal cancer patients who approved to receive preoperative chemoradiotherapy were studied. We prospectively collected biopsy specimens during colonoscopic examination from rectal cancer before starting preoperative chemoradiotherapy. Specimens from tumors were snap-frozen in liquid nitrogen and stored at -80 C until use. Paralleled tumor specimens were formalin fixed and paraffin embedded for histologic examination and other specimens were used for RNA extraction. RNA was extracted from tumor tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. All patients received a total dose of 50.4 Gy of radiation, UFT(300-500mg/day) and LV (75mg/day) and underwent standardized curative resection, following an interval of 4 weeks after chemoradiotherapy.
2013-01-29 | E-GEOD-35452 | biostudies-arrayexpress
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.
2015-01-27 | GSE65270 | GEO
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes. In order to determine how host gene expression might influence, or be influenced by the tissue associated microbiome, we analyzed 205 IPAA patients with biopsies collected from the pouch and afferent limb for host transcriptomics and 16S rDNA gene sequencing. Metadata included antibiotic use, inflammation score, and clinical classification. To achieve power for a genome-wide microbiome-transcriptome association study, we used principal component analysis to reduce OTUs and host transcripts to eigengenes and eigenclades explaining 50% of observed variance. These were subsequently tested for significant covariation with one another and/or outcome using multivariate linear modeling.
2015-01-27 | E-GEOD-65270 | biostudies-arrayexpress
Project description:Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma
| PRJNA1069754 | ENA
Project description:Anal cancer is a leading neoplasia in people with immune impartments populations, and the lack of an accurate screening test challenges its prevention. Because the bacteria living in the anal epithelium the anal microbiota seems to influence and be influenced by cancer development, specific patterns of anal microbes could help in the diagnosis of precancerous anal lesions. We aimed to discover microbial biomarkers of anal precancer in high-risk populations. We discovered 12 proteins, previously reported to be associated with cancer progression, that were more abundant in the anal bacterial from subjects with precancerous lesions.
2022-12-11 | PXD037268 | Pride