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Spatiotemporally Deciphering the Unknown Role of Persistent HPV Infection in Precancer to Cervical Cancer Progression: Integrating Single-Cell RNA-Sequencing Landscape and Spatial Transcriptomics Atlas [scRNA-seq]

ABSTRACT: Spatiotemporally Deciphering the Unknown Role of Persistent HPV Infection in Precancer to Cervical Cancer Progression: Integrating Single-Cell RNA-Sequencing Landscape and Spatial Transcriptomics Atlas [scRNA-seq]

PROVIDER: PRJNA860568 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20330700_1.fastq.gz	Fastqsanger.gz
	SRR20330700_2.fastq.gz	Fastqsanger.gz
	SRR20330701_1.fastq.gz	Fastqsanger.gz
	SRR20330701_2.fastq.gz	Fastqsanger.gz
	SRR20330702_1.fastq.gz	Fastqsanger.gz

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Spatiotemporally Deciphering the Unknown Role of Persistent HPV Infection in Precancer to Cervical Cancer Progression: Integrating Single-Cell RNA-Sequencing Landscape and Spatial Transcriptomics Atlas [Spatial Transcriptomics]

Project description:The mechanism underlying the cervical carcinogenesis mediated by persistent HPV infection remains elusive. Here we pioneeringly deciphered both temporal transition and spatial distribution of the cellular subsets during the disease progression from normal cervix, precancer lesions to cervical cancer by integrating scRNA-seq with ST. We not only identified three ‘HPV-related epithelial clusters’ unique to normal, HSIL and cervical cancer respectively, but also discovered node genes which potentially determined the disease progression. Moreover, we observed a gradual transition of multiple immune cells from positive immune response to dysregulation and exhaustion, to an immune-suppressive microenvironment during the malignant program. Besides, the cellular interaction analysis further verified a ‘homeostasis-balance-malignancy’ change within cervix microenvironment during disease escalation. Together, these findings not only deciphered mysterious persistent HPV infection spatiotemporally from the process of precancer to cervical cancer but also provided unprecedented possibilities for accurate diagnosis, precise treatment and prognosis evaluation for precancer and cervical cancer.

2023-04-02 | GSE208654 | GEO

2023-04-02 | GSE208653 | GEO

Project description:Spatiotemporally Deciphering the Unknown Role of Persistent HPV Infection in Precancer to Cervical Cancer Progression: Integrating Single-Cell RNA-Sequencing Landscape and Spatial Transcriptomics Atlas [Spatial Transcriptomics]

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Gene expression of CD66 expressing cells in cervical precancer cell line

Project description:Gene Expression profiles of sorted CD66High and CD66Low cells were generated from CIN612-9E cells grown in Emedia. We have analyzed the gene expression pattern of CD66High and CD66Low cells from CIN612 9E. These cells are derived from a cervical precancer lesion (M. Bedell, J. Hudson, T. Golub et al, 1991, J. Virol) Two sets of experiments (biological replicates) were performed for CD66High and CD66Low cells.

2014-09-30 | E-GEOD-59322 | biostudies-arrayexpress

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

Project description:BackgroundThe mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive.AimsHere, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer.Materials & methodsWe generated scRNA-seq profiles and spatial transcriptomics data from nine patient samples, including two HPV-negative normal, two HPV-positive normal, two HPV-positive HSIL and three HPV-positive cancer samples.ResultsWe not only identified three 'HPV-related epithelial clusters' that are unique to normal, high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune-suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a 'homeostasis-balance-malignancy' change occurred within the cervical microenvironment during disease progression.DiscussionWe for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV-related cervical oncogenesis, including normal, HPV-positive normal, HSIL and cancer. We identified three unique HPV-related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation.ConclusionTogether, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

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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.

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Gene expression of CD66 expressing cells in cervical precancer cell line

2014-09-30 | GSE59322 | GEO

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

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

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

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