The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer

Int J Med Sci. 2024 Apr 29;21(6):1176-1186. doi: 10.7150/ijms.95490. eCollection 2024.

Abstract

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

Keywords: JAK-STAT-SOCS1 Axis; Penile Cancer.

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Janus Kinases* / metabolism
  • Lymphatic Metastasis* / genetics
  • Lymphatic Metastasis* / pathology
  • Male
  • Penile Neoplasms* / genetics
  • Penile Neoplasms* / metabolism
  • Penile Neoplasms* / pathology
  • STAT4 Transcription Factor* / genetics
  • STAT4 Transcription Factor* / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein* / genetics
  • Suppressor of Cytokine Signaling 1 Protein* / metabolism
  • Tumor Microenvironment / immunology

Substances

  • SOCS1 protein, human
  • STAT4 protein, human