Genome-wide association study of cervical cancer in East Asian populations
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ABSTRACT:
PROVIDER: EGAS00001003199 | EGA |
REPOSITORIES: EGA
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Project description:Human papillomavirus (HPV) infection related malignancy remains a severe public health problem worldwide, although HPV prophylactic vaccine has been introduced 15 years ago . HPV-associated cancers comprise 29.1% of all 2.2 million infection-related cancers, including nearly 100% of cervical cancers1 and some head and neck cancers . Cervical cancers are the 3rd most common cancer in women worldwide, HPV16 and 18 account for about 70% of cervical cancers. Moreover, high-risk HPV infection, especially HPV16 infection, is related to a proportion of head and neck epithelial carcinoma in both developed and undeveloped countries. HPV related cancers are most severe in developing countries where HPV prophylactic vaccination rates are low.In this project, we use iTRAQ8plex-labelling proteomics to comparatively study the protein contents in the tumour tissues of early and late stage cervical cancer patietns.
2023-01-26 | PXD029103 | Pride
Project description:LncRNAs have been found to regulate mRNA expression levels and serve an important role in cervix carcinogenesis. To explore the lncRNA expression profiles during the development and progression of cervical cancer, we performed microarray analysis with total RNA in with only Human papillomavirus (HPV) 16-positive, 7 stage IA-IIA SCC (following the International Federation of Gynecology and Obstetrics (FIGO) criteria (10)) and 7 matched normal controls (NC).
2022-11-22 | GSE218460 | GEO
Project description:In most cases human papillomavirus (HPV) infections are cleared from the cervical cells by the immune system itself, but in a few cases, where there is persistent HPV infection, it can lead to cervical intraepithelial neoplasia (CIN) progression and ultimately invasive cervical carcinoma. The cytopathic effect is in general accompanied by chronic inflammation, which produces inflammation cytokines that contribute to DNA damage, and at the same time, aberrations occurred in the host DNA repair mechanisms, thus lead to HPV genomic integration into the host cells which propels cell immortalization. In this study, we reported the genome-wide expression profiles of both microRNAs (miRNAs) and mRNAs from 24 cervical samples with consecutive stages of normal, CIN I (mild dysplasia) and CIN III (severe dysplasia and carcinoma in situ), and presented the SIG++ algorithm which is founded on the evolution process of intermolecular regulation change during disease progression, to identify the significant change of miRNA-mRNA regulations rather than the expression change, across different disease stages, thereupon elucidating the molecular mechanisms of increasing host genomic instability as disease progresses. As reconstructing miRNA differential networks, we found that at each stage of CIN, there respectively exists specific miRNA regulations mediating chronic inflammation persistence, genome instability and cell survival, which coordinately carrys out the integration of HPV genomes into the host cell genomes, and finally results in cell immortalization. Beyond the specific implications for cervical carcinogenesis, this work establishes a new framework for studying the biology of miRNAs in pathogenesis from the perspective of miRNA differential regulation, and helps ensure the comprehensiveness of miRNA-mediated genetic regulatory pathways.
2013-11-02 | GSE51993 | GEO
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a “pooling” strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in an independent set of serum from patients with cervical cancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer. The panel of six proteins showed 72 % sensitivity and 82 % specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, e.g. squamous cell carcinoma antigen fail to show any discrimination.
2014-10-06 | PXD001055 | Pride
Project description:<p>Cervical cancer is responsible for 10-15% of cancer related deaths in women worldwide. The etiological role of infection with high-risk human papilloma viruses (HPV) in carcinomas of the cervix is well established. In general, the development of cervical carcinomas follows a progression from persistent HPV infection through precancerous lesions to invasive cancer. Previous studies have implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as chromosome-arm level copy number alterations in the pathogenesis of cervical carcinomas. Here, we report whole exome sequencing analysis of 118 cervical carcinoma-normal paired samples from patients in Norway and Mexico, as well as transcriptome sequencing of 80 cases and whole genome sequencing of 13 tumor-normal pairs. Novel somatic mutations include recurrent E322K substitutions in the MAPK1 gene encoding the ERK2 kinase and inactivating mutations in the HLA-B gene. In addition, recurrent somatic mutations in FBXW7, EP300, and NFE2L2 are novel in the context of primary cervical carcinomas. Analysis of HPV integration sites revealed recurrent integration into the RAD51B locus as well as co-occurrence of HPV genome integration and copy number gains within several genomic loci. These findings shed new light on the pathogenesis of cervical carcinomas and suggest potential novel therapeutic targets.</p>
| phs000600 | dbGaP
Project description:<p>Introduction: Cervical cancer is the fourth most common malignancy in women and is primarily caused by persistent infection with high-risk human papillomavirus (HPV). In addition, host immune responses, genetic factors, and lifestyle habits also have etiological roles. The cervicovaginal microbiome undergoes dynamic changes during menopause, which may be involved in the progression of cervical neoplasia. We aimed to elucidate the association between cervical microenvironmental changes and the progression of cervical neoplasia before and after menopause by integrating analyses of the cervical microbiome, related metabolites, cytokines, and microRNAs. Methods: A total of 248 HPV-positive women with cervical neoplasia, including 17 with cervical intraepithelial neoplasia (CIN1), 80 with CIN2, 82 with CIN3, and 69 with squamous cell carcinoma (SCC), were enrolled. As normal controls, 48 HPV-negative healthy women were included. Each group was stratified based on the mean menopausal age of 50 years. Cervical mucus was analyzed according to the methods outlined below. The microbiota was profiled by 16S rRNA gene sequencing, metabolites were analyzed by ultra-HPLC-tandem mass spectrometry, RT-qPCR was used for miRNA expression analysis, and RANTES levels were quantified by multiplex bead array. Data analysis was performed using MicrobiomeAnalyst and MetaboAnalyst.Results: In the SCC group, Prevotella and Atopobium were the key bacterial genera among the younger group, while Peptoniphilus, Fusobacterium, and Porphyromonas were more prevalent in elderly group (LDA score > 4.5). We observed a consistent positive correlation between Atopobium and xanthine in younger groups with CIN2 or worse (p < 0.0001). However, no such correlations were detected in elderly women. In addition, Atopobium, Adlercreutzia, and Gardnerella showed significant positive correlation with nicotinic acid in younger women with SCC compared to the elderly women (p < 0.0001). In the younger SCC women, several metabolites were significantly elevated in groups with high expression levels of RANTES, miR-20b-5p, and miR-155-5p.The cervical microbiome undergoes changes during menopause, and may influence disease progression by interacting with metabolites, cytokines, and miRNAs. These results highlight the potential for personalized medicine for cervical cancer that is tailored to different age groups.Please update the study abstract/description</p>
2025-07-07 | MTBLS12691 | MetaboLights
Project description:In most cases human papillomavirus (HPV) infections are cleared from the cervical cells by the immune system itself, but in a few cases, where there is persistent HPV infection, it can lead to cervical intraepithelial neoplasia (CIN) progression and ultimately invasive cervical carcinoma. The cytopathic effect is in general accompanied by chronic inflammation, which produces inflammation cytokines that contribute to DNA damage, and at the same time, aberrations occurred in the host DNA repair mechanisms, thus lead to HPV genomic integration into the host cells which propels cell immortalization. In this study, we reported the genome-wide expression profiles of both microRNAs (miRNAs) and mRNAs from 24 cervical samples with consecutive stages of normal, CIN I (mild dysplasia) and CIN III (severe dysplasia and carcinoma in situ), and presented the SIG++ algorithm which is founded on the evolution process of intermolecular regulation change during disease progression, to identify the significant change of miRNA-mRNA regulations rather than the expression change, across different disease stages, thereupon elucidating the molecular mechanisms of increasing host genomic instability as disease progresses. As reconstructing miRNA differential networks, we found that at each stage of CIN, there respectively exists specific miRNA regulations mediating chronic inflammation persistence, genome instability and cell survival, which coordinately carrys out the integration of HPV genomes into the host cell genomes, and finally results in cell immortalization. Beyond the specific implications for cervical carcinogenesis, this work establishes a new framework for studying the biology of miRNAs in pathogenesis from the perspective of miRNA differential regulation, and helps ensure the comprehensiveness of miRNA-mediated genetic regulatory pathways. There are totally 24 clinical samples in this study comprises three stages: 7 normal cervix samples (HPV-), 9 CIN I samples (HPV+) and CIN III samples (HPV+), where normal refers to the adjacent tissue of early lesions. For each sample, its total RNA was extracted and purified, then separately hybridized to Illumina HumanHT-12 V4.0 expression beadchip (gene symbol) and Illumina Human v2 MicroRNA Expression BeadChip, for examining the expression profiles of mRNAs and miRNAs, respectively.
2013-11-02 | E-GEOD-51993 | biostudies-arrayexpress
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a â??poolingâ?? strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of a new of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in a new set of 48 CIN, 50 CES, 34 CLS and 48 healthy controls as well as 49 serum samples from patients with ovarian cancer. The panel of six proteins showed 62% sensitivity and 82 % specificity for discrimination of patients with CIN grade 2 or worse from healthy controls, a stage of the disease where current protein-based biomarkers fail to show any discrimination.
2016-07-19 | MSV000079925 | MassIVE
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a “pooling” strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of a new of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in a new set of 48 CIN, 50 CES, 34 CLS and 48 healthy controls as well as 49 serum samples from patients with ovarian cancer. The panel of six proteins showed 62% sensitivity and 82 % specificity for discrimination of patients with CIN grade 2 or worse from healthy controls, a stage of the disease where current protein-based biomarkers fail to show any discrimination.
2014-10-06 | PXD001034 | Pride
Project description:Women persistently infected with human papillomavirus (HPV) type 16 are at high risk for development of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+). We aimed to identify biomarkers for progression to CIN3+ in women with persistent HPV16 infection. In this prospective study, 11,088 women aged 20–29 years were enrolled during 1991-1993, and re-invited for a second visit two years later. Cervical cytology samples obtained at both visits were tested for HPV DNA by Hybrid Capture 2 (HC2), and HC2-positive samples were genotyped by INNO-LiPA. The cohort was followed for up to 19 years via a national pathology register. To identify markers for progression to CIN3+, we performed microarray analysis on RNA extracted from cervical swabs of 30 women with persistent HPV16-infection and 11 HPV-negative women. After further validation, we found that high mRNA expression levels of TMEM45A, SERPINB5 and p16INK4a were associated with increased risk of CIN3+ in persistently HPV16-infected women.
2016-01-01 | GSE75132 | GEO