A hypoxia-derived gene signature to suggest cisplatin-based therapeutic responses in patients with cervical cancer

Jin Fang ¹, Ying Wang ¹, Chen Li ^1,2

⁰Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510613, China.

Computational and Structural Biotechnology Journal +

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July 10, 2024

View abstract on PubMed

Summary

This study developed a hypoxia-related gene signature to predict cervical cancer response to cisplatin. Fostamatinib shows promise as a treatment for cisplatin-resistant cervical cancer.

Area Of Science

Oncology
Molecular Biology
Genetics

Background

Cervical cancer is a global health issue with significant cisplatin resistance.
Hypoxia, common in cervical tumors, drives resistance to cisplatin therapy.
Predicting treatment response and identifying alternatives for resistant cases are critical.

Purpose Of The Study

To develop a hypoxia-inducible factor-1 (HIF-1)-related risk score (HRRS) model for predicting cisplatin efficacy in cervical cancer.
To identify novel therapeutic strategies for cisplatin-resistant cervical cancer.
To validate HIF-1 related genes as prognostic biomarkers for cisplatin responsiveness.

Main Methods

Utilized Cox and LASSO regression analyses on clinical data to build the HRRS model.
Employed quantitative reverse transcription PCR (qRT-PCR) to validate HIF-1 gene expression.
Investigated the efficacy of fostamatinib in vitro and in vivo in cervical cancer models.

Main Results

A hypoxia-related gene signature (HRRS) was established to predict cisplatin response.
Nine HIF-1 related genes were validated as predictors of cisplatin responsiveness.
Fostamatinib demonstrated significant anticancer effects in high HRRS cervical cancer cell lines and xenografts.

Conclusions

The developed HRRS model effectively predicts cisplatin response in cervical cancer.
Fostamatinib is identified as a potential therapeutic agent for cisplatin-resistant cervical cancer.
Targeting hypoxia-related pathways offers a promising avenue for overcoming treatment resistance.

Keywords:

Cervical cancer Cisplatin resistance Fostamatinib HIF-1 Hypoxia