Single-cell RNA-sequencing reveals the landscape of cervical cancer heterogeneity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168652 | GEO | 2021/05/12
REPOSITORIES: GEO
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Project description:Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome (scRNA-seq) analysis of CC cells and microenvironment has not been conducted. In this study, a total of 6 samples (3 CC and 3 adjacent normal tissues) were examined by scRNA-seq. Here, we performed single-cell RNA sequencing (scRNA-seq) to survey the transcriptomes of 57,669 cells derived from three CC tumors with paired normal adjacent non-tumor (NAT) samples. Single-cell transcriptomics analysis revealed extensive heterogeneity in malignant cells of human CCs, wherein epithelial subpopulation exhibited different genomic and transcriptomic signatures. We also identified cancer-associated fibroblasts (CAF) that may promote tumor progression of CC, and further distinguished inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF). CD8+ T cell diversity revealed both proliferative (MKI67+) and non-cycling exhausted (PDCD1+) subpopulations at the end of the trajectory path. We used the epithelial signature genes derived from scRNA-seq to deconvolute bulk RNA-seq data of CC, identifying four different CC subtypes, namely hypoxia (S-H subtype), proliferation (S-P subtype), differentiation (S-D subtype), and immunoactive (S-I subtype) subtype. Our results lay the foundation for precision prognostic and therapeutic stratification of CC.
2022-10-04 | E-MTAB-11948 | biostudies-arrayexpress
Project description:A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis. The meta-analysis including our results and data emerge from other available studies on gynecological malignancies and other cancer types, revealed common properties among them including deregulation of cell cycle, immune response, antiviral response and apoptosis.
2015-07-26 | GSE63678 | GEO
Project description:A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis. The meta-analysis including our results and data emerge from other available studies on gynecological malignancies and other cancer types, revealed common properties among them including deregulation of cell cycle, immune response, antiviral response and apoptosis. Total RNA was extracted from physiological and cancer patients from cervix, endometrium and vulvar tissue and was hybridized on Affymetrix HG133_A_2.0 microarray chips corresponding to more than 12.000 uniquely represented genes. A total of 35 samples were used to identify potential biomarkers and signatures in each type of cancer.
2015-07-26 | E-GEOD-63678 | biostudies-arrayexpress
Project description:Recurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of genomic copy number alterations, we surveyed genetic lesions in CC utilizing single nucleotide polymorphism (SNP) array. We identified specific genetic alterations associated with CC. These data will be useful in identification of target altered genes, novel markers for predicting high risk precancerous lesions to invasive cancer, comparison of copy number alterations with gene expression changes can provide gene targets for pharmacologic intervention. We demonstrate specific regions of gene amplification (e.g., 11q22), copy number gains (e.g., 3q, 5p, and 20q), and deletions (e.g., 2q, 11q23) in the present study, which forma a framework for identification of critical genes in CC tumorigenesis. Keywords: Cervical cancer, copy number alterations, HPV type, gene amplification
2008-06-04 | GSE10092 | GEO
Project description:Cervical cancer (CACX) is the tumor of the uterine cervix and its primary etiological factor is the infection of high risk human papilloma virus (hrHPV), primarily HPV16 and HPV18. CACX is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. In India, CACX accounts for approximately 1,22,844 new cases and 67,477 deaths annually. It is evident that Indian women are getting diagnosed at invasive stages of CACX leading to poor prognosis. Here, we tried to understand the change in the expression profile during the development of the tumor starting from HPV-negative normal samples to invasive CACX samples and try to understand the pathogenesis of cervical carcinoma in Indian patients.
2021-05-25 | GSE122697 | GEO
Project description:Cancer of the uterine cervix (CACX) is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. In India, CACX accounts for approximately 1,22,844 new cases and 67,477 deaths annually. Previously, we catalogued global copy-number aberrations [GSE76911] and performed gene expression profiling [GSE122697] in CACX. Interestingly, differential change in the expression between normal and tumor tissues of several genes did not correlate with the chromosomal copy-number alteration. This encouraged us to perform genome-wide DNA methylation analysis. Hence, in the current study, we discover the global methylation in cervical tumors at different clinical stages and HPV-negative normal ectocervix along with HPV16-positive cervical squamous cell carcinoma cell line, SiHa.
2024-03-12 | GSE168841 | GEO
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:We performed a comprehensive proteogenomic profiling of cervical cancer (CC) tumors obtained from 139 Chinese women. This study provides a valuable public resource including proteomic, phosphoproteome, acetylproteome for researchers and clinicians to delve deeper into molecular causes of CC, and to identify potential treatments and advance clinical practice.
2024-10-09 | PXD055203 | Pride
Project description:Affymetrix-U133-plus2.0-based gene expression analysis of laser-captured epithelium from 128 cervical tissue specimens from women enrolled in SUCCEED Cervical cancer (CC) is the second most frequent cancer in women and the third leading cause of cancer death in women worldwide. Our analysis of normal, precancerous, and cancerous cervical tissue shows that progress of the disease is a cascade of increased DNA replication/repair and cell proliferation followed by substantial metabolic shifts. The data show a sharp decrease in estrogen receptor alpha (ERα) in tumor cells, and ranking tissue specimens by estrogen-responsive gene expression correlates remarkably closely with histological pathology. Johan, den Boon, Morgridge Institute for Research at University of Wisconsin-Madison Paul, Ahlquist, Howard Hughes Medical Institute and Morgridge Institute for Research at University of Wisconsin-Madison Nicolas, Wentzensen, National Cancer Institute
2015-07-01 | GSE63514 | GEO
Project description:Dysregulation of glyco-gene expression in cancer can lead to aberrant glycans and glycoconjugates, which in turn can promote tumorigenesis. Cervical cancer display augmentation of aberrant sialylated glycans and increase of glyco-genes, which encoded enzymes participate in the sialylation pathways. Besides sialiltranferases, other glyco-genes, analyzed individually are reported as altered in cervical cancer. Here we show a comprehensive analysis of glyco-gene expression in cervical cancer to obtain a wide scenery of global changes in glycosylation pathways. First, we compared glyco-gene expression between normal tissue and cervical cancer. Second, we analyzed the glycogene expression in subtypes of cc to obtain hallmarks of glyco-gene expression in each case. Our results indicate that in cervical cancer the GPI-anchored biosynthesis is increased in cc while the synthesis of chondroitin and dermatan sulfate are decreased. Moreover, data show that adenocarcinoma displayed a homogenous glyco-gene expression pattern, where chondroitin /dermatan sulfate and heparan sulfate glycogenes are decreased, while keratan sulfate genes are increased. Dysregulation of glyco-gene expression in cancer can lead to aberrant glycans and glycoconjugates, which in turn can promote tumorigenesis. Cervical cancer display augmentation of aberrant sialylated glycans and increase of glyco-genes, which encoded enzymes participate in the sialylation pathways. Besides sialiltranferases, other glyco-genes, analyzed individually are reported as altered in cervical cancer. Here we show a comprehensive analysis of glyco-gene expression in cervical cancer to obtain a wide scenery of global changes in glycosylation pathways. First, we compared glyco-gene expression between normal tissue and cervical cancer. Second, we analyzed the glycogene expression in subtypes of cc to obtain hallmarks of glyco-gene expression in each case. Our results indicate that in cervical cancer the GPI-anchored biosynthesis is increased in cc while the synthesis of chondroitin and dermatan sulfate are decreased. Moreover, data show that adenocarcinoma displayed a homogenous glyco-gene expression pattern, where chondroitin /dermatan sulfate and heparan sulfate glycogenes are decreased, while keratan sulfate genes are increased.
2020-10-24 | GSE159976 | GEO