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NF-κB (p65, p50), IL-18, and IL-10 as Therapeutic Targets in Prostate Cancer and BPH: Molecular Insights into
Shailendra Dwivedi1, Sapna Saini1, Ajay -2
1Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Uttar Pradesh, 273008, India.
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.
Insights
Inflammation markers, Nuclear factor kappa B (NF-κB) and cytokines IL-18/IL-10, are elevated in prostate cancer. These biomarkers may aid in diagnosing and staging prostate cancer, especially in those with occupational exposures.
Area of Science:
- Oncology and Immunology
- Molecular Biology
Background:
- Prostate cancer is a leading malignancy in men, with chronic inflammation and environmental factors implicated in its development.
- Nuclear factor kappa B (NF-κB) and cytokines IL-18/IL-10 are key inflammatory mediators, but their role in benign prostatic hyperplasia (BPH) and occupation-related prostate cancer risk is understudied.
Purpose of the Study:
- To investigate the expression of NF-κB subunits (p65, p50) and cytokines (IL-18, IL-10) in prostate cancer, BPH, and healthy individuals.
- To examine the association of these markers with prostate cancer stage, metastatic status, and occupational exposures.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and ELISA were used to analyze mRNA and protein levels of NF-κB and cytokines in 664 participants (285 prostate cancer, 94 BPH, 285 controls).
- Statistical analyses, including two-way ANOVA and correlation analysis, were performed to assess group differences and relationships between markers and clinical factors.
Main Results:
- NF-κB p65/p50 and IL-18/IL-10 were significantly upregulated in prostate cancer versus BPH and controls (p < 0.0001).
- Biomarker expression correlated positively with advanced cancer stage and metastatic status.
- Tannery workers showed the highest expression; significant positive correlations were observed between NF-κB subunits and cytokines.
Conclusions:
- NF-κB and its downstream cytokines (IL-18, IL-10) show potential as noninvasive, inflammation-driven biomarkers for prostate cancer.
- These markers may assist in diagnosis, staging, and risk stratification, particularly for individuals with environmental or occupational exposures.
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