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.
Project description:To identify genomic alterations in uterine cervical carcinoma of Indian patients. Cancer of the uterine cervix (CACX) is the fourth most frequent carcinoma among women worldwide. In India, it accounts for approximately 132,000 new cases and 74,000 deaths annually contributing to nearly 1/3rd of the global cervical cancer deaths. Although, several etiological factors such as use of oral contraceptives, precocious marriage, multiparity, smoking etc. are seen to modify the risk of CACX, but infection by high risk human papillomavirus (hrHPV) is thought to be the major cause. Interestingly, long latency period for malignant outcome in only a subset of HPV-infected women indicates involvement of additional chromosomal alterations.Since the first report of changes in chromosomal content of CACX, several genome-wide studies reported frequent chromosomal gain of 3q (3q24–29), 1q (1q22–q23, 1q25.3–q32.1) and 5p (5p12–p13) and loss of 3p (3p12–23), 11q (11q22.3–25) and 4p (4p16.3–p16.1). But no study was done to catalogue the precise genomic alterations in CACX of Indian patients. To the best of our knowledge, for the first time the present study revealed precise chromosomal aberrations with differential frequency in Indian CACX patients (n=11). Among these alterations, frequent (>50%) amplifications of distinct chromosomal loci were as follows: 1p36.11-1p31.1, 1q21.1-1q44, 3q13.13-3q29, 5p15.33-5p12, 8q24.3, 16q22.2, 19q13.13-19q13.2, Xp22.33-Xp11.21 and Xq11.2-Xq12. While recurrent (>35%) loss at chromosomal loci, 2q34-2q37.3, 4p16.3-4p12, 4q21.3, 8p23.3, 8p23.2, 8p11.22, 11q14.1-11q25, 13q13.3-13q14.3, and 19p13.3 were also observed. All CACX patients showed precise amplification of chromosome 3 at coordinates 3q25.2-3q26.1 (chr3:154427429-162796745), 3q26.1-3q26.31 (chr3:162901354-175146595) and 3q26.32-3q29 (chr3:175208719-198094926). Highest (72%) loss of chromosomal loci 11q24.3-11q25 (chr11:128926744-135034169) was seen.
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.
Project description:We found miRNA expression profiling of uterine cervical squamous cell carcinoma by miRNA microarray and validated the genes as clinical significance of squamous cell carcinoma, especially in metastasis.
Project description:This is a study indented to investigate the alterations in the molecular profile of cervix uteri, as it progresses thorough various FIGO stages of carcinoma, by means of global gene expression profiling, in a cohort of Indian patients. In addition expresion profiles of early and advanced stage cervical cancer were compared to identify biomarkers and therapeutic targets for the advanced stages. Cervical cancer and non-malignant cervical tissues are obtained from consenting patients following hospital ethics committee approved protocols. The samples are profiled against universal Human reference RNA from Stratagene on 19K EST microarrays from Microarray Center, University Health Network, Toronto, Canada. Biological replicates: Normal = 4; Cervical cancer Stage I = 8; Cervical cancer Stage II = 9; Cervical cancer Stage III = 8. One replicate per array.
Project description:This is a study indented to investigate the alterations in the molecular profile of cervix uteri, as it progresses thorough various FIGO stages of carcinoma, by means of global gene expression profiling, in a cohort of Indian patients. In addition expresion profiles of early and advanced stage cervical cancer were compared to identify biomarkers and therapeutic targets for the advanced stages.
Project description:Analysis of various of up-regulated and down-regulated genes in Normal Cervical mucosa, Cervical intraepithelial neoplasia and Cervical squamous cell carcinoma. The report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of cervical mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Microarray based study of global gene expression is often used to extract molecular signatures underlying cancer progression. Such endeavors endorse self organizing map, a type of artificial neural network to analyze high dimensional pre-processed transcriptome data to segregate hotspot genes in component plane for disease subtypes. This report provides a data analysis methodology for identification of coexpressed gene patterns, as emerging clusters, in global transcriptome of oral and cervical mucosal premalignant and malignant conditions in comparison to their normal counterparts. Four exclusive cluster patterns, each involving 100 − 300 genes, were identified from component planes for oral study groups. Gene expression associated with each pattern belonged to 32 biological processes. Analysis on cervical biopsies, where cancer was compared to cervical interepithelial neoplasia and normal counterpart, it revealed three non-overlapping patterns for each condition. In cervical interepithelial neoplasia an intermediate pattern with nine different dominant functional processes was identified, whereas, in cervical squamous cell carcinoma pattern showed dominance for seven different functions. This analysis demonstrated utility of self organizing map to capture dominant enriched patterns as visual plots and revealed six common biological processes like transcription and RNA processing, cytoskeleton reorganization, angiogenesis, immunity, neuron signalling, and connective tissue remodelling in the pathogenesis of oral and cervical cancers. In fact it could provide an intuitive understanding of molecular course in carcinogenesis and may contribute for combinatorial biomarker discovery.