Cytokine Signatures for Lung Cancer Diagnosis in African American Populations

Abstract

Lung cancer is the leading cause of cancer-related deaths among both men and women. African Americans (AAs) experience disproportionately higher incidence and mortality compared to other ethnic groups. Cytokines play multifaceted and crucial roles in the initiation, progression, and spread of cancer. Our aim was to identify cytokine biomarkers for the early detection of lung cancer in AAs. We examined eight key cytokines (Interleukin-1, IL-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)) in the plasma of 104 lung cancer patients and 48 cancer-free individuals using the FirePlex Immunoassay. These findings were subsequently validated in a separate cohort of 58 cases and 58 controls. IL-8, IFN-γ, and TNF-α exhibited elevated levels in both AA and White American (WA) lung cancer cases. Notably, IL-10 and MCP-1 displayed significant increases specifically in AA lung cancer patients, with MCP-1 levels associated with lung adenocarcinoma cases. Conversely, WA lung cancer patients showed heightened IL-6 levels, particularly linked to lung adenocarcinoma. The combined use of specific cytokines showed promise in lung cancer diagnosis, with IL-8, IL-10, and MCP-1 achieving 76% sensitivity and 79% specificity in AAs and IL-6 and IL-8 combined offering 76% sensitivity and 74% specificity in WAs. These diagnostic biomarkers were validated in the independent cohort. The ethnicity-related cytokine biomarkers hold promise for diagnosing lung cancer in AAs and WAs, potentially addressing the observed racial disparity.

Keywords: African Americans; biomarkers; cytokines; lung cancer; plasma.

Figure 1

Cytokine levels in plasma of AA and WA lung cancer patients compared to their respective control groups. WA lung cancer patients exhibited significantly increased levels of IL-6 in contrast to their controls. IL-8, IFN-γ, and TNF-α displayed elevated expression levels in both AA and WA lung cancer patients compared to their respective control groups. IL-10 and MCP-1 showed exclusive upregulation in AA lung cancer cases when compared to their counterparts. *, p < 0.01.

Figure 2

Receiver operating characteristic (ROC) curve analysis for individual cytokines and their combinations in distinguishing NSCLC patients from cancer-free smokers of different ethnicities. The area under the curve (AUC) reflects the overall diagnostic accuracy of these biomarker panels. (A) Combined utilization of IL-8, IL-10, and MCP-1 for the diagnosis of NSCLC in AAs. (B) Combined application of IL-6 and IL-8 for the diagnosis of NSCLC in WAs.