Assessment of Serum Interleukin-38 Levels in Iranian Patients with Benign and Malignant Salivary Gland Cancers: A Case-Control Study

Background: Similar to other cancers, the development of salivary gland cancers (SGCs) is influenced by the tumor microenvironment and controlled by the host’s immune system. Interleukin-38 (IL-38) is highly expressed in inflammatory conditions to prevent excessive inflammatory responses and tissue injury; however, its role in SGCs remains unclear. This study aimed to evaluate IL-38 serum levels in Iranian patients with benign and malignant SGCs and in healthy individuals to explore its potential as a diagnostic biomarker for SGCs. Methods: In this retrospective cross-sectional study, IL-38 levels were measured in serum samples from 120 patients with SGCs (64 benign and 56 malignant cases) and 60 age- and sex-matched healthy control participants using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: There was a significant difference in IL-38 serum levels between patients and the control group (49.1±6.2 ng/L vs. 38.6±6.8 ng/L, P<0.0001), but not between benign and malignant cases (48.2±7.1 ng/L vs. 50.2±4.8 ng/L, P=0.085). A significant negative correlation was observed between SGC size and IL-38 serum levels (R=−0.195, P=0.042). However, IL-38 was not associated with other clinicopathologic factors, including gender, age, tumor type, lesion location, and tumor stage (P>0.05). Conclusion: This study, for the first time, supports the clinical value of IL-38 serum levels as a valuable biomarker for diagnosing patients with SGCs. Focusing on IL-38 production or its release mechanism could offer therapeutic benefits for these patients. However, further research with a larger sample is required.