Inflammatory cytokines and non-small cell lung cancer in a CT-scan screening cohort: Background review of the literature

Article type: Research Article

Authors: DeCotiis, Christopher^a | Hu, Yingjie^c | Greenberg, Alissa K.^a | Huie, Maryann^a | Tsay, Jun-Chieh J.^a | Pass, Harvey^b | Goldberg, Judith D.^c | Rom, William N.^{a; *}

Affiliations: [a] Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY, USA | [b] Division of Thoracic Surgery, Department of Cardiothoracic Surgery, New York University School of Medicine, New York, NY, USA | [c] Division of Biostatistics, Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA

Correspondence: [*] Corresponding author: William N. Rom, MPH Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, Bellevue Hospital, NBV 7N24, New York, NY 10016, USA. Tel.: +1 212 263 6479; Fax: +1 212 263 8442; E-mail:william.rom@nyumc.org

Abstract: BACKGROUND: Inflammatory cytokines are at the intersection of tumor cell biology and host immune response. Peripheral cytokine expression levels may reflect the microscopic tumor milieu, and specific cytokines play an integral role in tumor initiation, growth, and metastasis. High-throughput cytokine analysis may identify panels for early-stage non-small cell lung cancer (NSCLC) diagnosis and identify individuals at high-risk for lung cancer with indeterminate lung nodules 8-20 mm in size. METHODS: Thirteen serum cytokines from the NYU Lung Cancer Biomarker Center cohort with early-stage NSCLC were analyzed using bead-based immunoassay technology. RESULTS: In the NYU cohort, a one unit increase in interferon-γ increased risk of lung cancer by 3% (OR = 1.03, 95% CI, 1.02-1.05) and a one unit increase in TNF-α decreased the risk of lung cancer by 53% (OR = 0.47, 95% Cl, 0.31-0.71) when both cytokines were included in a logistic regression model with adjustments for age and pack-years of smoking. The resulting AUC for the Receiver Operating Characteristic (ROC) curve was 0.88; the sensitivity and specificity at the optimal cutpoint were 78.9% and 90.3%, respectively. CONCLUSIONS: Cytokines have limited value in the early diagnosis of early-stage NSCLC. Our review of the literature suggests that although inflammation is important for the development of NSCLC, that cytokines are increased in more advanced lung cancer than when the diagnosis occurs at presentation.

Keywords: Inflammatory cytokines, biomarkers, non-small cell lung cancer

DOI: 10.3233/CBM-150559

Journal: Cancer Biomarkers, vol. 16, no. 2, pp. 219-233, 2016