NF-κB (p65, p50), IL-18, and IL-10 as Therapeutic Targets in Prostate Cancer and BPH: Molecular Insights into Inflammation-Driven Pathogenesis

Document Type : Research Articles

Authors

1 Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Uttar Pradesh, 273008, India.

2 Department of Anaesthesia, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Uttar Pradesh, 273008, India.

3 Department of Radiotherapy, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Uttar Pradesh, 273008, India.

4 Department of Pathology, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Uttar Pradesh, 273008, India.

5 Department of Urology, King George’s Medical University, Lucknow, Uttar Pradesh 226003, India.

6 Principal, Maharaja Suhel Dev Autonomous State Medical College & Mahrishi Balark Hospitals, Bahraich, Uttar Pradesh 271801, India.

Abstract

Background: Prostate cancer is a significant global health burden and is the second most commonly diagnosed malignancy among men. Chronic inflammation and environmental exposures, including occupational toxins, are increasingly recognized as key contributors to its development. Nuclear factor kappa B (NF-κB) subunits p65 and p50, along with the cytokines IL-18 and IL-10, are central mediators of inflammation, but remain understudied in the context of benign prostatic hyperplasia (BPH) and occupation-related risks. This study investigates the expression patterns of these markers in prostate cancer, BPH, and healthy individuals, and examines their association with disease stage and occupational exposure. Methods: A total of 664 participants were enrolled, including 285 prostate cancer patients, 94 BPH cases, and 285 healthy controls. Peripheral blood samples were collected and analyzed for mRNA expression using quantitative real-time PCR (qRT-PCR), and for protein levels using ELISA. Statistical comparisons among groups and two-way ANOVA were performed to evaluate the effects of disease status and occupation. Correlation analysis was used to assess the associations between NF-κB and cytokine levels. Results: NF-κB p65 and p50, as well as IL-18 and IL-10, were significantly upregulated in prostate cancer compared to BPH and controls (p < 0.0001). Expression levels increased with cancer stage and metastatic status. Among occupational groups, tannery workers exhibited the highest biomarker expression. Significant positive correlations were found between NF-κB subunits and both cytokines. Conclusion: NF-κB and its downstream cytokines, IL-18 and IL-10, may serve as inflammation-driven, noninvasive biomarkers for prostate cancer diagnosis, staging, and risk stratification, particularly in populations exposed to environmental factors.

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