Open Access

ARTICLE

MAPK9 as a therapeutic target: unveiling ferroptosis in localized prostate cancer progression

by CHENG-GONG LUO^1,2,#, JIAO ZHANG^1,#, YUN-ZHAO AN¹, XUAN LIU¹, SHUAI-JIE LI¹, WEI ZHANG¹, KAI LI¹, XU ZHAO¹, DONG-BO YUAN¹, LING-YUE AN¹, WEI CHEN², YE TIAN^1,*, BIN XU^1,*

1 Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, China
2 Department of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

* Corresponding Authors: YE TIAN. Email: ; BIN XU. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Advances in Biomarker Research: Unveiling the Pathways to Precision Medicine)

BIOCELL 2024, 48(5), 771-792. https://doi.org/10.32604/biocell.2024.048878

Received 21 December 2023; Accepted 23 February 2024; Issue published 06 May 2024

Abstract

Background: Ferroptosis, a lipid peroxidation-mediated programmed cell death, is closely linked to tumor development, including prostate cancer (PCa). Despite established connections between ferroptosis and PCa, a comprehensive investigation is essential for understanding its impact on patient prognosis. Methods: A risk model incorporating four ferroptosis-related genes was developed and validated. Elevated risk scores correlated with an increased likelihood of biochemical recurrence (BCR), diminished immune infiltration, and adverse clinicopathological characteristics. To corroborate these results, we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort (TCGA) and the Gene Expression Synthesis Cohort (GEO). Moreover, we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays, as well as animal studies conducted in vivo. Additionally, we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis. Results: The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients. Mitogen-activated protein kinase 9 (MAPK9) emerged as a crucial gene within the model. In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation. Conclusion: The findings provide a novel perspective for advancing ferroptosis exploration in PCa, bridging basic research and clinical applications.

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Keywords

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Supplementary Material

Supplementary Material File

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