Evaluation of IL-22, IL-33, and IL-38 in Small-Cell and Non-Small-Cell Lung Cancer and Their Association with Histopathological and Immunohistochemical Markers

Abstract

Introduction: Lung cancer is the leading cause of cancer deaths worldwide. Lung cancer is divided into two categories, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), apart from different cellular origin, their biological behavior, therapeutic response and clinical outcome also vary. Interleukins like IL-22, IL-33, and IL-38 were recently reported to play an important role in inflammation and tumor progression. The purpose of this study was to measure the serum levels of these interleukins in lung cancer patients according to the histological type and treatment status and to correlate with the clinicopathological parameters.

Materials and Methods: A case–control study was conducted at the Oncology Teaching Hospital in Baghdad from December 2024 to June 2025. The study included 180 participants: 120 patients with histologically confirmed lung cancer 24 with SCLC and 96 with NSCLC and 60 healthy controls. Among patients, 48 were newly diagnosed and untreated, while 72 had received treatment. Serum concentrations of IL-22, IL-33, and IL-38 were measured using enzyme-linked immunosorbent assay and were correlated with histological subtypes and immunohistochemical markers, including thyroid transcription factor-1, Cytokeratin-7 (CK-7), Kiel 67 antigen (Ki-67), and synaptophysin.

Results: IL-22 showed the highest levels in treated NSCLC, particularly in squamous cell carcinoma. IL-33 showed the highest levels in untreated adenocarcinoma. IL-38 showed a distinct pattern in squamous cell carcinoma.

Conclusion: Different levels of IL-22, IL-33, and IL-38 in lung cancer subtypes and groups indicate that these may be immunological biomarkers for monitoring these cancers or response to treatment.