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Updated: Jun 27, 2025

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
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The Genomic, Transcriptomic, and Immunologic Landscape of HRAS Mutations in Solid Tumors

Samuel A Kareff1, Asaad Trabolsi1, Harris B Krause2

  • 1Department of Graduate Medical Education, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33136, USA.

Cancers
|April 27, 2024
PubMed

Insights

This study explores HRAS-mutant (HRASmt) cancers, revealing distinct molecular profiles and immune cell changes. HRASmt tumors are linked to poorer survival in head and neck cancers, guiding future targeted therapy development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • HRAS mutations (HRASmt) are rare but significant in certain cancers.
  • Tipifarnib is a targeted therapy for HRAS-mutant head and neck squamous cell carcinoma (HNSCC).
  • Understanding HRASmt tumor biology is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the molecular co-alterations, immune profiles, and clinical outcomes of HRAS-mutant (HRASmt) solid tumors.
  • To analyze HRASmt prevalence across various cancer types, including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC.
  • To explore the tumor microenvironment (TME) and survival implications of HRASmt.

Main Methods:

  • Retrospective analysis of 524 HRASmt solid tumors.
  • Comparison of molecular and immune profiles between HRASmt and HRAS wild-type (HRASwt) tumors.
  • Survival analysis for HRASmt across different cancer types.

Main Results:

  • HRASmt was most frequent in UC (3.0%) and HNSCC (2.82%), absent in Her2+ BC.
  • HRASmt was associated with squamous histology in NSCLC and altered TME, including increased M1 macrophages in UC, HNSCC, and TNBC.
  • HRASmt correlated with shorter overall survival in HNSCC (p=0.003) but not other cancers.

Conclusions:

  • HRASmt solid tumors exhibit unique molecular and immune characteristics.
  • HRASmt is a significant negative prognostic factor in HNSCC.
  • These findings offer insights for novel therapeutic targets and clinical trial design in HRASmt cancers.
Keywords:
HRASbiomarkersprecision oncologytipifarnibtranslational oncology

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