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Genome-wide microRNA profiling of HPV-positive self-samples: Promising triage markers for early detection of cervical cancer

ABSTRACT: Genome-wide microRNA profiling of HPV-positive self-samples: Promising triage markers for early detection of cervical cancer

PROVIDER: PRJNA413777 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6153960.fastq.gz	Fastqsanger.gz
	SRR6153970.fastq.gz	Fastqsanger.gz
	SRR6153980.fastq.gz	Fastqsanger.gz
	SRR6153990.fastq.gz	Fastqsanger.gz
	SRR6154000.fastq.gz	Fastqsanger.gz

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Genome-wide microRNA profiling of HPV-positive self-samples: Promising triage markers for early detection of cervical cancer

Project description:Offering self-sampling for HPV testing improves the effectiveness of current cervical screening programs. Molecular triage markers directly applicable on self-samples are needed to further stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. MicroRNAs (miRNAs) deregulation has been implicated in the development of cervical cancer, and represents a potential class of triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self-samples. This study is the first to establish genome-wide miRNA profiles in HPV-positive self-samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self-samples. Small RNA sequencing (sRNA-Seq) was conducted to determine genome-wide miRNA expression profiles in 73 HPV-positive self-samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRidge, a penalized method on logistic regression. Classification of sRNA-Seq data yielded a panel of 9 miRNAs with a combined Area Under the Curve (AUC) of 0.89 for CIN3 detection. Six out of nine miRNAs were validated by qPCR in 165 independent HPV-positive self-samples and resulted in a combined AUC of 0.72 for CIN3+ detection. This study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected in HPV-positive self-samples using genome-wide miRNA profiling. Further validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self-samples.

2018-01-01 | GSE104758 | GEO

Identification and validation of a novel 3-gene methylation classifier for HPV-based cervical screening on self-samples

Project description:Background: Offering self-sampling of cervico-vaginal material for human papillomavirus (HPV) testing is an effective method to increase the coverage in cervical screening programmes. Molecular triage directly on HPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a methylation classifier for detection of precancer (CIN3) or cancer, applicable to self-samples obtained by different devices. Findings: Genome-wide DNA methylation profiling of HPV-positive self-samples revealed 12 methylation targets for CIN3 detection. Multiplex quantitative methylation-specific PCR of these targets yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5), showing a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. All self-samples from women with cervical cancer scored methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on self-samples from HPV-positive women.

2018-01-01 | GSE99511 | GEO

MicroRNA analysis in HPV-positive and HPV-negative cervical cancer cell lines

Project description:Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tumors. MiRNA expression profile was investigated by microrray analysis in the HPV-positive cervical cancer cell lines SiHa (HPV16-positive cell line derived from a cervical squamous cell carcinoma), CaSki (HPV16-positive cell line derived from a metastatic cervical epidermoid carcinoma), and HeLa (HPV18-positive cell line derived from a cervical adenocarcinoma) and compared with primary HFKs and C33a (HPV-negative cervical cell line).

2018-01-16 | E-MTAB-6361 | biostudies-arrayexpress

HPV genome expression at invasive cervical carcinomas infected by multiple HPV genotypes

Project description:Multiple HPV genotypes infection is frequently detected in HPV+ cervical lesions, however it is not well stablished how is the different viral interaction during the carcinogenic process. Here we carried out a comprehensive study to characterize the multiple HPV genome expression and integration by RNA-Seq analysis in 19 invasive cervical carcinomas with HPV coinfections. Analysis of tumoral DNA by a hybridization kit indicated multi-infection ranging from 2 to 6 different HPV genotypes, without a preferential species coinfection. The expression analysis showed that a single HPV genotype preferentially expressed its genome, might indicating a competition between the infecting virus. Finally, the search for HPV/human chimeric transcripts indicated integration from just one HPV in almost all samples, corroborating the expression findings.

2021-07-28 | GSE144293 | GEO

miRNA expression profiles of HPV-infected cervical cancer patients in the Uyghur population in China

Project description:The study examined the infection state of HPV in the Uyghur population with cervical cancer, followed by genotyping to determine the variation in the types of HPV. Using microRNA microarray technology, differential gene expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined. The microarray results were verified by qRT-PCR using 20 sets of HPV-infected cervical cancer and uninfected cervical tissues.

2016-08-27 | GSE86100 | GEO

Nuclear Lactate Dehydrogenase A Senses ROS to Produce α-Hydroxybutyrate for HPV-Induced Cervical Tumor Growth

Project description:It is well known that high-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and E7 was identified as one of the key initiators in HPV-mediated carcinogenesis. Here we show that lactate dehydrogenase A (LDHA) preferably locates in the nucleus in HPV16-positive cervical tumors due to E7-induced intracellular reactive oxygen species (ROS) accumulation. Surprisingly, nuclear LDHA gains a non-canonical enzyme activity to produce α-hydroxybutyrate and triggers DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation, resulting in the activation of antioxidant responses and Wnt signaling pathway. Furthermore, HPV16 E7 knocking-out reduces LDHA nuclear translocation and H3K79 tri-methylation in K14-HPV16 transgenic mouse model. HPV16 E7 level is significantly positively correlated with nuclear LDHA and H3K79 tri-methylation in cervical cancer. Collectively, our findings uncover a non-canonical enzyme activity of nuclear LDHA to epigenetically control cellular redox balance and cell proliferation facilitating HPV-induced cervical cancer development.

2018-09-24 | PXD011058 | Pride

Detection of cervical intraepithelial neoplasia and HPV infection in women with inflammatory bowel disease

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

Single Cell Dissection of Transcriptional Heterogeneity in HPV Positive and Negative Cervical Cancer

Project description:Here we performed single-cell RNA sequencing of more than 30,000 of cells from HPV16+ and HPV- cervical cancer patients. We comprehensively revealed the heterogeneity of both the malignant cell populations and immune lineages in HPV+ and HPV- CC, as well as the cellular crosstalks with potential relevance to tumor progression. Moreover, our results demonstrated that distinct interaction patterns in HPV+ and HPV- groups could mediate similar functions or pathways, and we further constructed a three-cell interaction resource.

2021-04-13 | GSE171894 | GEO

HPV Infection and Cervical Neoplasm in Women With Inflammatory Bowel Disease: a Cross-sectional Study

Project description:The associations between female inflammatory bowel disease (IBD) patients and human papilloma virus (HPV) infection and cervical neoplasia (dysplasia or cancer) were unclear. Especially there was no data for Chinese IBD population. So we investigated the incidence and risk factors of HPV infection and cervical neoplasia (dysplasia or cancer) in female IBD patient.

| 2236852 | ecrin-mdr-crc

Identification of markers associated with deregulated hTERT during HPV-medaited transformation

Project description:Although high-risk human papillomavirus (HPV) infection plays a major role in the development of cervical cancer, additive oncogenic events are involved as well. One key event involves increased activity of telomerase resulting from a deregulated expression of its catalytic subunit hTERT. Our previous microcell-mediated chromosome transfer studies revealed that introduction of human chromosome 6 in the HPV16 immortalized keratinocyte cell line FK16A and in the HPV16 containing cervical cancer cell line SiHa induced growth arrest, resulting from a repression of hTERT mRNA expression and telomerase activity. Here, this model was used to analyze expression profiles associated with hTERT deregulation in HPV transformed cells. Microarray expression analysis of 12 FK16A/chromosome 6 hybrids, four of which were negative for endogenous hTERT and 8 of which were positive for endogenous hTERT, resulted in the identification of 164 differentially expressed genes. Differential expression of a selection of 5 genes was verified by real-time RT-PCR. Of these 164 genes, 32 were also differentially expressed in other HPV transformed cells with deregulated hTERT. For 2 of these genes, encoding AQP3 and MGP, altered expression in hTERT positive cervical carcinomas was confirmed by real-time RT-PCR and immunohistochemistry, respectively. In summary we identified 32 candidate biomarkers for deregulated hTERT mRNA expression which may enable the identification of cervical premalignant lesions that are at highest risk to progress to invasive cancer. Keywords: microarray expression analysis, hTERT, cervical cancer

2008-06-25 | GSE8288 | GEO

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