# Integrative Analysis of Shared Pathogenic Genes and Potential Mechanisms in Gardnerella vaginalis and Persistent HPV16 Infection

## TL;DR

This study explores shared genes and mechanisms between Gardnerella vaginalis overgrowth and persistent HPV16 infection, identifying potential biomarkers for cervical cancer.

## Contribution

The study integrates transcriptomic data to identify shared pathogenic genes and mechanisms between Gardnerella vaginalis and HPV16 infection.

## Key findings

- 74 common differentially expressed genes were identified between GV infection and HPV16 persistence.
- RSAD2 and IFIT1 were identified as central hub genes with potential diagnostic and therapeutic value.
- Single-cell transcriptomics revealed distinct expression patterns of RSAD2 and IFIT1 in immune and epithelial cells during cervical cancer progression.

## Abstract

Bacterial vaginosis, often accompanied by Gardnerella vaginalis (GV) overgrowth, is associated with persistent high-risk human papillomavirus (HR-HPV) infection, particularly HPV16. This study integrated transcriptomic data from in vitro GV infection experiments and a GEO dataset (GSE75132) of HPV16 persistence to elucidate shared pathogenic mechanisms. Differential expression analysis identified 4115 genes modulated by GV infection and 861 by HPV16 persistence, with 74 common differentially expressed genes (DEGs) displaying consistent trends. Enrichment analyses revealed that these DEGs participate in metabolic pathways, immune defense, host–pathogen interactions, and carcinogenesis. Protein–protein interaction networks and Random Forest (RF) feature selection pinpointed radical S-adenosyl methionine domain containing 2 (RSAD2) and Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) as central hub genes. Upstream transcription analysis identified the homer_AGTTTCAGTTTC_ISRE motif and established a ceRNA network involving hsa-miR-654-5p, IFIT1/RSAD2, and lncRNAs. Mendelian randomization (MR) and colocalization analyses linked RSAD2 downregulation to an increased risk of cervical carcinoma in situ (rs2595163, PPH4 = 0.62), while ROC analysis demonstrated strong diagnostic potential for the combined hub gene expression. Notably, single-cell transcriptomics revealed distinct RSAD2 and IFIT1 expression patterns in immune and epithelial cells during the progression from HPV infection to cervical cancer. Collectively, these findings support RSAD2 and IFIT1 as promising biomarkers and therapeutic targets for HPV-related cervical lesions.