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.

Project description:<p>Introduction: Cervical cancer is the fourth most common malignancy in women and is primarily caused by persistent infection with high-risk human papillomavirus (HPV). In addition, host immune responses, genetic factors, and lifestyle habits also have etiological roles. The cervicovaginal microbiome undergoes dynamic changes during menopause, which may be involved in the progression of cervical neoplasia. We aimed to elucidate the association between cervical microenvironmental changes and the progression of cervical neoplasia before and after menopause by integrating analyses of the cervical microbiome, related metabolites, cytokines, and microRNAs. Methods: A total of 248 HPV-positive women with cervical neoplasia, including 17 with cervical intraepithelial neoplasia (CIN1), 80 with CIN2, 82 with CIN3, and 69 with squamous cell carcinoma (SCC), were enrolled. As normal controls, 48 HPV-negative healthy women were included. Each group was stratified based on the mean menopausal age of 50 years. Cervical mucus was analyzed according to the methods outlined below. The microbiota was profiled by 16S rRNA gene sequencing, metabolites were analyzed by ultra-HPLC-tandem mass spectrometry, RT-qPCR was used for miRNA expression analysis, and RANTES levels were quantified by multiplex bead array. Data analysis was performed using MicrobiomeAnalyst and MetaboAnalyst.Results: In the SCC group, Prevotella and Atopobium were the key bacterial genera among the younger group, while Peptoniphilus, Fusobacterium, and Porphyromonas were more prevalent in elderly group (LDA score > 4.5). We observed a consistent positive correlation between Atopobium and xanthine in younger groups with CIN2 or worse (p < 0.0001). However, no such correlations were detected in elderly women. In addition, Atopobium, Adlercreutzia, and Gardnerella showed significant positive correlation with nicotinic acid in younger women with SCC compared to the elderly women (p < 0.0001). In the younger SCC women, several metabolites were significantly elevated in groups with high expression levels of RANTES, miR-20b-5p, and miR-155-5p.The cervical microbiome undergoes changes during menopause, and may influence disease progression by interacting with metabolites, cytokines, and miRNAs. These results highlight the potential for personalized medicine for cervical cancer that is tailored to different age groups.Please update the study abstract/description</p>

Project description:Background. MicroRNAs (miRNAs) are short (~22 nt) non-coding regulatory RNAs that control gene expression at the translational level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. This prompted the development of miRNA-chips for cancer diagnosis or prognosis, opening a new door to understand carcinogenesis. Cervical cancer is one of the most common cancers in women worldwide. Therefore, there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform developed in house containing probes for mature miRNAs. Results. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, miRNAs deregulation in malignant and pre-malignant cervical tissues was detected after tackling the high variability observed. We were also able to identify putative targets of relevant candidate miRNAs. Conclusions. Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, deregulated miRNAs highlight new candidate targets allowing a better understanding of the molecular mechanism of this tumour type. In this study we used a common reference design experiment where the common reference used was a commercial RNA from normal cervix (Ambion) and the test samples were 4 pre-treatment squamous cell cervical carcinoma, 7 high-grade Squamous Intraepithelial Lesion (CINII, n=2 and CIN III, n=5) sample, 9 low-grade Squamous Intraepithelial Lesion (CIN I) samples, 19 normal cervix samples and 4 pools of normal cervix samples.

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