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Bimodal genomic approach predicting Semaphorin 7A (SEMA7A) as prognostic biomarker in adrenocortical carcinoma

Biorxiv : the Preprint Server for Biology +

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April 28, 2025

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April 28, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

High SEMA7A gene expression in adrenocortical carcinoma (ACC) indicates a poor prognosis. SEMA7A may be a potential therapeutic target and a biomarker for ACC patients, correlating with steroidogenesis and MAPK signaling pathways.

Area Of Science

  • Endocrinology
  • Oncology
  • Genomics

Background

  • Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mortality.
  • Limited reliable biomarkers exist for predicting ACC patient outcomes and guiding therapy.
  • The rarity of ACC restricts the scope of clinical trials.

Purpose Of The Study

  • To elucidate the genetic underpinnings of ACC by analyzing transcriptome data.
  • To identify potential prognostic biomarkers and therapeutic targets in ACC.
  • To investigate the role of SEMA7A in ACC biology and its association with clinical outcomes.

Main Methods

  • Transcriptome analysis (RNA-Seq) of 112 ACC tumor samples from TCGA and NCI.
  • Gene expression analysis focusing on bimodally expressed genes, particularly SEMA7A.
  • Immunohistochemistry (IHC) staining to correlate gene and protein expression.
  • Correlation analyses with steroidogenesis and signaling pathways (integrin, FAK, MAPK/ERK).

Main Results

  • High SEMA7A gene expression is significantly associated with poor prognosis in ACC (hazard ratio = 4.27; p < 0.001).
  • SEMA7A expression is elevated in hormone-producing ACCs and correlates with steroidogenesis genes (e.g., CYP17A1, CYP11A1).
  • SEMA7A is co-expressed with integrin-β1, FAK, and MAPK/ERK signaling pathways.
  • IHC confirmed a significant correlation between SEMA7A RNA-Seq and protein expression.

Conclusions

  • SEMA7A is a potential prognostic biomarker for ACC patients.
  • Elevated SEMA7A expression suggests increased tumor risk and potential for targeted immunotherapies.
  • SEMA7A warrants further research as a candidate for ACC therapy and biomarker development.