Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma

Cancer Immunol Immunother. 2024 Dec 30;74(1):38. doi: 10.1007/s00262-024-03870-8.

Abstract

Background: Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth.

Methods: We analyzed 1,374 colon adenocarcinoma samples from the TCGA and GEO datasets. Our approach involved bioinformatics to uncover how HNF1B influences immunotherapy and the immune microenvironment, with corroboration from external databases and experimental validation.

Results: HNF1B was expressed at low levels in colon adenocarcinoma and was linked to patient prognosis. CIBERSORT, TIME, and GSVA analyses revealed that HNF1B was associated with macrophage infiltration, immune checkpoints, and signaling pathways. Drug prediction suggested a negative relationship between HNF1B and EGFR-targeted therapies, implying potential resistance. Validation with external cohorts confirmed that patients with low HNF1B expression experienced less benefit from immunotherapy.

Conclusion: This study clarifies the role of HNF1B in the treatment of colon adenocarcinoma. This study provides a foundation for further in-depth mechanistic studies and proposes new directions for optimizing immunotherapy strategies for colon adenocarcinoma.

Keywords: Colorectal adenocarcinoma; Hepatocyte nuclear factor-1β; Immune checkpoint blockade; Immunotherapy; Tumor microenvironment.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / immunology
  • Adenocarcinoma* / therapy
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Clinical Relevance
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / immunology
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Colonic Neoplasms* / therapy
  • Computational Biology / methods
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 1-beta* / genetics
  • Hepatocyte Nuclear Factor 1-beta* / metabolism
  • Humans
  • Immunotherapy* / methods
  • Multiomics
  • Prognosis
  • Tumor Microenvironment* / immunology

Substances

  • Hepatocyte Nuclear Factor 1-beta
  • Biomarkers, Tumor
  • HNF1B protein, human