A Role of Serum Interleukin-39 and Association with Small and Non-Small Cell Carcinoma in Lung Cancer Patients

Document Type : Research Articles

Authors

1 Department of Chemistry, Faculty of Science, University of Kufa, Najaf 54001 Iraq.

2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Kufa, Najaf 54001, Iraq.

3 Microbiology Department, College of Veterinary Medicine, AL-Qasim Green University, Babylon 51013, Iraq.

4 College of Pharmacy, Al-Zahraa University for Women, Karbala, Iraq.

5 Department of Chemistry, College of Science, University of Al-Qadisiyah, Al Diwaniyah, Iraq.

6 College of Veterinary Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq.

Abstract

Background: Lung cancer is the second most common malignancy globally and the leading cause of cancer-related deaths. Interleukin-39 (IL-39), a member of the IL-12 family secreted by B cells, acts as a pro-inflammatory cytokine and induces IL-23p19 expression in endothelial cells. Recent findings suggest reduced IL-39 expression in autoimmune thyroid disorders and breast cancer, indicating its possible role in disease progression. Aim of Study: To evaluate the role of IL-39 as an early prognostic biomarker in lung cancer. Materials and Methods: A case-control study was conducted between February and September 2024, involving 180 individuals aged 45–77. The cohort included 90 lung cancer patients (45 with small-cell carcinoma and 45 with non-small cell carcinoma) and 90 healthy controls. Blood samples were analyzed using ELISA to quantify IL-39 and additional tests, including CBC, liver enzymes (ALT, AST, ALP), and lipid profile (cholesterol, triglycerides). Statistical analysis was performed to assess correlations and diagnostic performance. Results: IL-39 levels were significantly lower in stage IV compared to stage III in both cancer types, with a greater reduction observed in small-cell carcinoma. Significant negative correlations were found between IL-39 and total cholesterol, NLR, ALT, AST, and ALP, while positive correlations were noted with hemoglobin and triglycerides. IL-39 demonstrated excellent diagnostic accuracy in small-cell carcinoma with a cut-off value of 3.26950 pg/mL (sensitivity 100%, specificity 100%, AUC 1.000). In non-small cell carcinoma, the cut-off value was 4.88700 pg/mL (sensitivity 63.5%, specificity 92.6%, AUC 0.689). Conclusion: IL-39 shows promise as a predictive and diagnostic biomarker in lung cancer, particularly in small-cell carcinoma, and may play a protective role in disease modulation through immune-related pathways.

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Articles in Press, Accepted Manuscript
Available Online from 12 September 2025
  • Receive Date: 08 February 2025
  • Revise Date: 02 June 2025
  • Accept Date: 10 September 2025