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Updated: Aug 26, 2025

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Investigation of molecular mechanisms underlying JAK/STAT signaling pathway in HPV-induced cervical carcinogenesis
Kulbhushan Thakur1, Divya Janjua1, Gauri Shishodia2,3
1Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, 110007, India.
Abstract:
The precise mechanism of action of Janus Kinases (JAK)/Signal Transducer and activator of Transcription (STAT) signaling in human papillomavirus (HPV)-associated cervical cancer (CaCx) is poorly defined. The present study dissected the underlying components of JAK/STAT signaling in HPV-positive cervical neoplasms. Whole transcriptome profile of CaCx cohort from TCGA database revealed elevated STAT3 and its impact on CaCx patients' survival. Using the RT2 Profiler PCR Array, we analyzed 84 genes of interest associated with JAK/STAT signaling in mRNA derived from HPV-negative and HPV-positive cervical lesions which revealed 21 differentially expressed genes (DEGs). Analyses of DEGs using the Database for Annotation, Visualization and Integrated Discovery tool indicated maximum genes enriched in immune response and negative regulation of apoptotic process. Protein-protein network analysis indicated IL4, STAT5A, STAT4, and JAK3 to be the key genes in the interaction network. Further, 7 key DEGs (IL4R, IRF1, EGFR, OAS1, PIAS1, STAT4, and STAT5A) were validated in TCGA cohort using R2 platform. These genes were differentially expressed among HPV-positive cervical tissues and their correlation with STAT3 was established. EGFR and IL4R showed a comparatively strong correlation with STAT3 that supports their involvement in pathogenesis of CaCx. Finally, the Kaplan-Meier analysis established the prognostic association of the key DEGs, in CaCx cohort. The STAT3 and associated key genes discovered from our study establish a strong pathogenic role of JAK/STAT3 pathway in HPV-mediated cervical carcinogenesis.
Insights
The JAK/STAT pathway, particularly STAT3, plays a key role in human papillomavirus (HPV)-associated cervical cancer. This study identified key genes involved in immune response and apoptosis, highlighting their prognostic significance in cervical carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The precise role of Janus Kinases (JAK)/Signal Transducer and activator of Transcription (STAT) signaling in human papillomavirus (HPV)-associated cervical cancer (CaCx) remains unclear.
- Understanding these pathways is crucial for developing targeted therapies against HPV-driven cancers.
Purpose of the Study:
- To investigate the JAK/STAT signaling pathway components in HPV-positive cervical neoplasms.
- To identify key genes and their correlation with STAT3 in the pathogenesis of cervical cancer.
- To establish the prognostic significance of identified genes in CaCx.
Main Methods:
- Analysis of whole transcriptome profiles from The Cancer Genome Atlas (TCGA) database for CaCx.
- Utilized RT2 Profiler PCR Array to analyze 84 JAK/STAT signaling genes in HPV-negative and HPV-positive cervical lesions.
- Employed bioinformatics tools (DAVID, R2 platform) for gene enrichment, network, and survival analyses.
Main Results:
- Elevated STAT3 expression was observed, correlating with poorer survival in CaCx patients.
- Identified 21 differentially expressed genes (DEGs) in HPV-positive lesions, enriched in immune response and apoptosis regulation.
- Protein-protein network analysis highlighted IL4, STAT5A, STAT4, and JAK3 as key interaction genes.
- Validated 7 key DEGs (IL4R, IRF1, EGFR, OAS1, PIAS1, STAT4, STAT5A), with EGFR and IL4R showing strong correlation with STAT3.
- Kaplan-Meier analysis confirmed the prognostic association of these key DEGs.
Conclusions:
- The JAK/STAT3 pathway is strongly implicated in the pathogenesis of HPV-mediated cervical carcinogenesis.
- STAT3 and its associated key genes (EGFR, IL4R) are critical players in CaCx development and progression.
- These findings provide potential therapeutic targets for HPV-associated cervical cancer.
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