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.

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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