Kruppel like factors family expression in cervical cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE89657 | GEO | 2016/11/09
SECONDARY ACCESSION(S): PRJNA352834
REPOSITORIES: GEO
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Project description:Cervical cancer is the fourth most common type of cancer is women worldwide,and it is a major cause of cancer-related deaths in developing countries. Despite the marked reduction oberved in the rates of this disease as a result of screening programs, it is necessary to develop robust biomarkers that can detect the neoplastic early in HPV-related cervical leisons. We performed comparative mRNA seqeuncing from exfoliative cervical cytology from nine Korean women on the Illumina NovaSeq6000 platforms. The pathological tissues mathced to the corresponding cytological samples were simulanously confirmed and were considered to be endpoint diagnosis. The pathological dianoses consisted of three cases of chronic cervicitis, 2 high-grade squamous intraepithelial leisons(HSILs), 2squamous cell carcinomas in situ(CIS); and 2 invasive quamous cell carcinomas (SQCCs), respectively. Using bioinformatics analyses, differentially expressed genes (DEGs; absolute fold change >1; p<0.05) were applied for Gene Ontology (GO), Gene Set EnrichmentAnalysis (GSEA), and protein-protein interaction (PPI) networks.
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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>
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Project description:Cervical cancers is the second most malignancy in women. It has been clinically important histological variants such as squamous cell carcinoma (SCC) and adenocarcinoma (AC) and adenosquamous carcinomas (ASC). It has been postulated that AC and ASC has a worse prognosis than pure SCC. However, many of the mixed or other types confuses its diagnosis and aggressive/resistant behavior of some tumors has resulted in debate for prognostic role of empirical pathological classification. In addition, the prognosis of adenosquamous carcinoma is still under debate. To establish a novel molecular classification of cervical cancer, we investigated intrinsic characteristics using expression profile.
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Project description:Cervical mucus is a viscous fluid functioning as a uterine cervix plug. It is formed and produced by cervical glands located in the cervix. During ovulation, cervical mucus starts to become less viscous, which is a good window for non-invasive sampling. Our study focuses on the proteomic characterization of cervical mucus, which may thus act as a non-invasively acquired source of biomarkers for diseases and physiological conditions of the female genital tract. Our study aimed at two aims - the first is to optimize a proteomic workflow of cervical mucus processing. The second aim is to assess differences in the proteomic composition of cervical mucus in natural ovulatory cycles and IVF cycles with controlled ovarian hyperstimulation. The sampling was done in cooperation with women undergoing intrauterine insemination in a natural ovulatory cycle and women undergoing controlled ovarian hyperstimulation for IVF. The optimization of proteomic workflow including an analysis on an Orbitrap mass spectrometer was performed. The results revealed the protein composition and the differences of the cervical mucus between natural and stimulated uterus.
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Project description:Cervical cancers is the second most malignancy in women. It has been clinically important histological variants such as squamous cell carcinoma (SCC) and adenocarcinoma (AC) and adenosquamous carcinomas (ASC). It has been postulated that AC and ASC has a worse prognosis than pure SCC. However, many of the mixed or other types confuses its diagnosis and aggressive/resistant behavior of some tumors has resulted in debate for prognostic role of empirical pathological classification. In addition, the prognosis of adenosquamous carcinoma is still under debate. To establish a novel molecular classification of cervical cancer, we investigated intrinsic characteristics using expression profile. A total of 80 cevical cancer samples of following histology were included in this study: 54 SCC, 18 ASC, 6 AC, and 2 others. Replicate number: 2. No control/no reference sample was included. One-color.
2010-09-28 | E-GEOD-20167 | biostudies-arrayexpress
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
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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.
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Project description:Cells located at the invasive front and in the tumor mass of mouse cervical squamous cell carcinomas were isolated by laser microdissection from hematoxylin-stained HPV/E2 sections. 7 months old HPV/E2 mice treated with oestrogen develop invasive cervical squamous cell carcinomas. This model recapitulates human invasive cervical neoplasias. We used microarrays to compare the transcriptome of cells located at the invasive front versus cells located in the tumor mass of mouse squamous cell carcinomas.
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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 20â29 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. We aimed at identifying genes differentially expressed in women with persistent HPV16 infection that either progressed to CIN3+ or not. As a test of principle we first compared HPV16 persistently infected women with HPV-negative women.
2016-07-03 | E-GEOD-75132 | biostudies-arrayexpress
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 (ER?) 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 24 normal, 14 CIN1 lesions, 22 CIN2 lesions, 40 CIN3 lesions, and 28 cancers specimens were cryosecrtioned and used for laser-capture, RNA extraction, two rounds of T7-mediated amplification, and cRNA biotinylation. Bio-cRNA was hybridized to Affymetrix U133-Plus2.0 arrays, scanned signals were processed through GC-RMA
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