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Comprehensive Transcriptomic Analysis and Biomarker Prioritization of Hydroxyprogesterone in Breast Cancer.

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Hydroxyprogesterone (HP) impacts breast cancer by altering gene expression in normal and tumor tissues. It activates metabolic pathways in normal tissue and influences cell junctions and extracellular matrix in tumors.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hydroxyprogesterone (HP) is a synthetic progestogen used in obstetrics.
  • Its effects on breast cancer biology are not fully understood.
  • Molecular mechanisms of HP in tumor tissue require further exploration.

Purpose of the Study:

  • Investigate gene expression changes related to HP in operable breast cancer.
  • Explore molecular mechanisms of HP's influence on breast cancer.
  • Identify potential biomarkers for HP's effects.

Main Methods:

  • Transcriptomic profiling was used to analyze gene expression.
  • Pre-operative exposure to 17α-HP caproate (17-OHPC) was administered.
  • Analysis focused on normal adjacent tissue (NAT) and tumor tissue.

Main Results:

  • In NAT, HP activated steroid-hormone and lipid/xenobiotic-metabolism programs, with crosstalk to PI3K-Akt and NF-κB pathways.
  • Tumor tissue showed dominant signals in tight-junction/apical-junction and ECM-receptor remodeling.
  • FKBP5 and CLDN4 were prioritized as key candidates, with TSPO and SGK1 as exploratory.

Conclusions:

  • HP influences breast cancer through distinct molecular pathways in normal and tumor tissues.
  • Findings suggest potential biomarkers (e.g., FKBP5, CLDN4) for HP's effects.
  • This study provides mechanistic insights and nominates candidates for future research.