Clinicopathological and prognostic significance of interleukin-8 expression and its relationship to KRAS mutation in lung adenocarcinoma

• Published in: British journal of cancer 2014-04, Vol.110 (8), p.2047-2053
• Main Authors: Sunaga, N, Kaira, K, Tomizawa, Y, Shimizu, K, Imai, H, Takahashi, G, Kakegawa, S, Ohtaki, Y, Nagashima, T, Kasahara, N, Kawashima, O, Hisada, T, Saito, R, Yamada, M
• Format: Article
• Language: English
• Subjects: 631/208/737; 631/67/395; 692/53/2422; 692/699/67/1612; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy; Cytokines; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Hospitals; Humans; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Kaplan-Meier Estimate; Kinases; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical prognosis; Medical sciences; Medicine; Metastasis; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasm Staging; Oncology; Pneumology; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Survival analysis; Thoracic surgery; Tumors; Tumors of the respiratory system and mediastinum; University graduates
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.110

Background: On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas. Methods: IL-8 expression was examined by quantitative RT–PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed. Results: IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers’ subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR / KRAS . Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8 . DFS and OS were significantly shorter in the patients with mutant KRAS /high IL-8 than in those with wild-type KRAS /low IL-8 . Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis. Conclusions: Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS -driven adenocarcinoma.