DNA Methylation Biomarkers for Cervical Cancer Risk Prediction in HIV-Positive Nigerian Women
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PROVIDER: PRJNA1175663 | ENA |
REPOSITORIES: ENA
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Project description:Cervical cancer (CC) remains a significant public health issue in low- and middle-income countries (LMICs), especially in Western sub-Saharan Africa and Nigeria. While global CC incidence and mortality have declined, these regions continue to face high rates due to inadequate screening and the high prevalence of HIV, which increases CC risk by promoting persistent HPV infections. This study aimed to identify DNA methylation (DNAm) biomarkers for cervical intraepithelial neoplasia (CIN) and CC in HIV-positive Nigerian women and to assess their potential for clinical risk prediction. From 2018 to 2020, 538 participants were recruited from Nigerian tertiary hospitals. Cervical tissue samples were analyzed for DNAm using the Infinium MethylationEPIC BeadChip array, and HPV genotyping was conducted via next-generation sequencing. An epigenome-wide association study revealed 24 significant DNAm biomarkers associated with CIN and CC. These biomarkers showed hypermethylation in tumor suppressor genes (e.g., PRMD8), hypomethylation in oncogenes (e.g., MIR520H), and aberrant methylation in genes related to HIV/HPV infection and oncogenesis (e.g., GNB5, LMO4, FOXK2, NMT1). A machine learning-based DNAm classifier achieved 92.9% sensitivity and 88.6% specificity in predicting CC risk, with higher risk observed in adjacent normal cervical samples from CIN/CC patients and HIV/HPV co-infected women. DNAm biomarkers offer a promising approach to enhancing CC screening and early detection, particularly for HIV-positive women in LMICs. The DNAm-based model developed in this study shows potential for more accurate CC risk stratification, highlighting the need for further optimization, validation, and implementation in low-resource settings.
2024-11-01 | GSE279982 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, with particularly high burdens among people living with HIV (PLWH) in low-resource settings like Nigeria. Effective early detection remains a major challenge due to limited access to imaging-based surveillance and the low sensitivity of current biomarkers such as alpha-fetoprotein (AFP). We conducted an epigenome-wide association study (EWAS) of circulating cell-free DNA (ccfDNA) methylation in a Nigerian cohort of HIV-positive individuals (n = 245), spanning HCC, cirrhosis, fibrosis, and HCC-free groups. Using random forest modeling, we developed and evaluated a ccfDNA methylation classifier (ccfDNAmRF) for HCC risk prediction. We identified 73 CpG sites significantly associated with HCC (false discovery rate <0.01). The ccfDNAmRF model demonstrated strong discriminatory power, achieving 100% sensitivity and 81–91% specificity for distinguishing HCC from cirrhosis, fibrosis, and HCC-free groups (area under the curve [AUC]: 92–97%). Combining ccfDNA methylation risk scores with AFP further improved classification accuracy (AUC up to 98.5%). Notably, ccfDNA methylation patterns displayed clear dose–response relationships across the disease spectrum, supporting their utility for early-stage detection and risk stratification. Our findings highlight the promise of ccfDNA methylation biomarkers as a minimally invasive, blood-based screening tool for improving early HCC detection among PLWH in resource-limited settings. These biomarkers may help address critical gaps in current surveillance strategies, offering scalable solutions adaptable to high-risk populations.
2025-06-25 | GSE298812 | GEO
Project description:For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid proteins that could predict imminent delivery in asymptomatic patients with a short cervix. An aptamer-based multiplex platform was used to profile 1,310 AF proteins, and the significance of protein dysregulation was determined by moderated t-tests between women who destined to deliver within two weeks of amnicentesis. The area under the receiver operating characteristic curve was calculated to determine whether protein abundance in combination with cervical length improved the prediction of imminent delivery after amnicentesis as compared to cervical length alone.
2022-09-26 | GSE186135 | GEO
Project description:Cervical cancer ranks as the first in cancer mortality among women of low-middle income countries, where 80% of the 570,000 cases and 311,000 worldwide deaths estimated for 2018 occurred (Ferlay et al. 2018 ). Persistent infections with high-risk HPV (hrHPV) genotypes can lead to high-grade cervical intraepithelial (CIN) grade 2 (CIN2) or higher, (CIN2+), if untreated, a high percentage of these lesions may progress to cancer. Despite its high sensitivity, the hrHPV test has low specificity to detect CIN2+ lesions given that a high percentage of women (80 %) infected with hrHPV genotypes will resolve the infection spontaneously. microRNAs (miRNAs) are small non-coding RNAs and their differential expression patterns seen to be associated with cervical intraepithelial lesions. Our work aimed to identify miRNAs differentially expressed in CIN2+ respect with <CIN1 and to evaluate their potential use as biomarkers to distinguish low- from high-grade lesions within hrHPV positive women. For our discovery set we used small RNA sequencing (miRNA-seq) to compare the miRNA expression patterns in 20 Formalin-Fixed Paraffin-Embedded (FFPE) tissues from hrHPV-positive women from Medellin, Colombia presenting low- (n=10) and high-grade lesions (n=10). Top five miRNAs presenting high fold change and low coefficient of variation were used validated by RT-PCR in our validation set composed 210 age-matched independent hrHPV-positive FFPE tissues, and an in-silico approach was used to understand the function of the differentially expressed miRNAs in the context of HPV infection.
2023-05-07 | GSE167858 | GEO
Project description:Circulating Cell-free DNA Methylation Biomarkers for Hepatocellular Carcinoma Risk Prediction in HIV-Positive Nigerian Population
| PRJNA1271421 | ENA
Project description:Schistosomiasis increases the risk of HIV acquisition in women, by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or S. mansoni infection using mucosal gene expression and cervicovaginal lavage cytokine levels. We recruited women with/without S. haematobium and with/without S. mansoni infections from separate villages in rural Tanzania, as determined by urine and stool microscopy and serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. In the S. haematobium village, 110 genes were differentially expressed in the cervical mucosa of women with (n=18) versus without (n=39) S. haematobium. Among the 27 cytokines analyzed in cervicovaginal lavage fluids, interleukin 15 (IL-15) was lower in women with S. haematobium (62.8 versus 102.9 pg/mL, adjusted p=0.0013). Differences were not observed in the S. mansoni setting between women with (n=11) or without (n=29) S. mansoni. We demonstrate altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni, which may impact HIV acquisition and cancer risks. Studies to determine effects of anti-schistosome treatment on these mucosal alterations are needed.
2019-12-21 | GSE142456 | GEO
Project description:Background: Non-coding RNA has been shown to participate in numerous biological and pathological processes and has attracted increasing attention in recent years. Recent studies have demonstrated that long non-coding RNA and microRNA can interact through various mechanisms to regulate mRNA. Yet the gene-gene interaction has not been investigated in cervical cancer of Uygur woman. High throughput sequencing were used to identify differentially expressed lncRNA, miRNA, and mRNA profiles between normal, cervical intraepithelial neoplasia and cervix carcinoma tissues. Gene Oncology (GO), KEGG enrichment analysis were performed. Gene co-expression network were constructed and pivotal genes were screened out. A total of 1464 lncRNAs were differentially expressed between normal, cervical intraepithelial neoplasia and cervical cancer tissues. GO and KEGG analysis show that related molecular mechanisms and biological processes play a role in cervical cancer. The gene-gene interaction network was constructed and visualized based on Pearson correlation coefficients and TargetScan prediction. These results have shown the potential of lncRNA, miRNA, and mRNA as clinical biomarkers and in elucidating pathological mechanisms of cervical cancer from a transcriptomic perspective.
2021-03-10 | GSE149763 | GEO
Project description:Interventions: Group 1: A PAP smear and HPV will be taken in women with inflammatory bowel disease
Primary outcome(s): Frequency of Cervical intraepithelial neoplasia and human paplloma Virus in women with inflammatory bowel disease
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: diagnostic
| 2431908 | ecrin-mdr-crc
Project description:Emerging biomarkers based on medical images and molecular characterization of tumor biopsies open up for combining the two disciplines and exploiting their synergy in treatment planning. We compared pretreatment classification of cervical cancer patients by two previously validated imaging- and gene-based hypoxia biomarkers, evaluated the influence of intratumor heterogeneity, and investigated the benefit of combining them in prediction of treatment failure. The imaging-based biomarker was hypoxic fraction, determined from diagnostic dynamic contrast enhanced (DCE)-MR images. The gene-based biomarker was a hypoxia gene expression signature determined from tumor biopsies. Paired data were available for 118 patients. Intratumor heterogeneity was assessed by variance analysis of MR images and multiple biopsies from the same tumor. The two biomarkers were combined using a dimension-reduction procedure. The biomarkers classified 75% of the tumors with the same hypoxia status. Both intratumor heterogeneity and distribution pattern of hypoxia from imaging were unrelated to inconsistent classification by the two biomarkers, and the hypoxia status of the slice covering the biopsy region was representative of the whole tumor. Hypoxia by genes was independent on tumor cell fraction and showed minor heterogeneity across multiple biopsies in 9 tumors. This suggested that the two biomarkers could contain complementary biological information. Combination of the biomarkers into a composite score led to improved prediction of treatment failure (HR:7.3) compared to imaging (HR:3.8) and genes (HR:3.0) and prognostic impact in multivariate analysis with clinical variables. In conclusion, combining imaging- and gene-based biomarkers enables more precise and informative assessment of hypoxia-related treatment resistance in cervical cancer, independent of intratumor heterogeneity.
2020-06-26 | GSE146114 | GEO
Project description:miRNAs signature as potential biomarkers for cervical precancerous lesions in Human Papillomavirus Positive women
| PRJNA705230 | ENA