Chao Li

Integrated miRNA‐mRNA Expression Profiles Revealing Key Molecules in Ovarian Cancer Based on Bioinformatics Analysis

Ovarian cancer is one of the leading causes of gynecological malignancy‐related deaths. The underlying molecular development mechanism has however not been elucidated. In this study, we used bioinformatics to reveal critical molecular and biological processes associated with ovarian cancer. The microarray datasets of miRNA and mRNA expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Besides, we performed target prediction of the identified differentially expressed miRNAs. The overlapped differentially expressed genes (DEGs) were obtained combined with miRNA targets predicted and the DEGs identified from the mRNA dataset. The Cytoscape software was used to design a regulatory network of miRNA‐gene. Moreover, the overlapped DEGs in the network were subjected to enrichment analysis to explore the associated biological processes. The molecular protein‐protein interaction (PPI) network was used to identify the key genes among the DEGs of prognostic value for ovarian cancer, and the genes were evaluated via Kaplan‐Meier curve analysis. A total of 186 overlapped DEGs were identified. Through miRNA‐gene network analysis, we found that miR‐195‐5p, miR‐424‐5p, and miR‐497‐5p highly exhibited targeted association with overlapped DEGs. The three miRNAs are critical in the regulatory network and act as tumor suppressors. The overlapped DEGs were mainly associated with protein metabolism, histogenesis, and development of the reproductive system and ocular tissues. The PPI network identified 10 vital genes that promote tumor progression. Survival analysis found that CEP55 and CCNE1 may be associated with the prognosis of ovarian cancer. These findings provide insights to understand the pathogenesis of ovarian cancer and suggest new candidate biomarkers for early screening of ovarian cancer.

Microbiome and metabolomic changes associated with HPV clearance in women undergoing local excisional treatment for cervical intraepithelial neoplasia

ABSTRACT Cervical intraepithelial neoplasia (CIN) is a common gynecological condition often associated with persistent human papillomavirus (HPV) infections. Although the loop electrosurgical excision procedure (LEEP) is effective in removing lesions, some patients remain HPV positive post-treatment. In this prospective study, we enrolled reproductive-age women diagnosed with HPV-related CIN and employed a multi-omics analysis of cervicovaginal secretion and cervical tissue microbiomes, alongside non-targeted and targeted metabolomic assessments. We aim to explore the role of the cervicovaginal and intratissue microbiota and associated metabolites on HPV clearance following LEEP. We observed significant shifts in bacterial diversity and composition in both cervicovaginal secretion and cervical tissue samples. Notably, distinct bacterial species, such as Lactobacillus and certain anaerobes (e.g., Prevotella bivia ), were correlated with HPV clearance post-LEEP. Metabolomic profiling revealed that the HPV-cleared group exhibited elevated acetic acid levels and significant alterations in glycerophospholipid metabolism, suggesting a potential role in promoting HPV clearance. Correlation analyses demonstrated significant associations between altered bacteria and metabolites with HPV status, with models incorporating both achieving high predictive accuracy. Overall, our findings highlight the importance of the cervicovaginal and intratissue microbiomes and metabolites in facilitating HPV clearance, suggesting potential therapeutic targets for patients with CIN. IMPORTANCE The clearance of human papillomavirus (HPV) after local excisional treatment for cervical intraepithelial neoplasia is crucial for patient health. This study reveals significant alterations in the cervicovaginal secretion and cervical tissue microbiomes, alongside metabolomic changes, which are associated with HPV clearance. Through a comprehensive multi-omics approach, we identified specific bacterial species and metabolic changes that correlate with successful HPV clearance post-loop electrosurgical excision procedure. Notably, the presence of beneficial Lactobacillus species and elevated levels of acetic acid linked to glycerophospholipid metabolism emerged as potential biomarkers for HPV status, suggesting that these factors play a pivotal role in improving treatment outcomes. These findings highlight the potential for microbiome-targeted therapies to enhance HPV clearance and provide insights into the microbial and metabolic mechanisms involved in cervical health.

Microbial and metabolic profiles associated with HPV infection and cervical intraepithelial neoplasia: a multi-omics study

ABSTRACT Cervical cancer is the most common malignancy of the female reproductive system, with the incidence of human papillomavirus (HPV) being a crucial factor in its pathogenesis. Emerging evidence indicates that cervicovaginal microbiota may influence HPV persistence and cervical intraepithelial neoplasia (CIN). However, the interplay between cervicovaginal and cervical tissue microbiomes and their association with HPV infection and CIN remains poorly understood. In this cross-sectional study, we analyzed the microbiota profiles of cervicovaginal and cervical tissue via five-region 16S rRNA gene metabarcoding, along with cervicovaginal metabolites, including short-chain fatty acids (SCFAs) and non-targeted metabolomic data, from 94 women. Key species, particularly Lacticaseibacillus and various anaerobes, are vital components of the microbiota found in both cervicovaginal secretions and cervical tissue, despite notable differences in microbial composition. The CIN group exhibited significant differences in microbial diversity and composition compared to the control groups, with key species such as Lacticaseibacillus iners and Prevotella bivia associated with HPV status and CIN progression. Metabolomic analysis revealed alterations in glycerophospholipid metabolism, but not in SCFAs, with correlations observed between metabolites and HPV status. Notable associations, including P. bivia –PE(18:1/0:0)–HPV and Fusobacterium periodonticum –PI(40:6)–HPV, were identified. Our findings emphasize the critical roles of cervicovaginal and cervical tissue microbiomes in HPV infection and CIN development, highlighting specific microbial species and metabolic pathways for early detection and therapeutic targets. IMPORTANCE Cervical cancer is the most prevalent malignancy in the female reproductive system, with human papillomavirus (HPV) persistency being a critical factor in its pathogenesis. This study highlights the significant yet often overlooked role of cervicovaginal secretion and cervical tissue microbiota in influencing HPV infection and the progression of cervical intraepithelial neoplasia (CIN). By employing a multi-omics approach, we elucidated distinct microbiota profiles in cervical tissues compared to cervicovaginal secretions, revealing a complex interplay between specific bacterial species (notably Lacticaseibacillus and anaerobes) and metabolomic changes associated with glycerophospholipid metabolism. Our findings address a significant gap in understanding the interplay between cervicovaginal secretion and cervical intratissue microbiomes, HPV infection, and CIN.