title: Clinicopathological and prognostic significance of interleukin-8 expression and its relationship to KRAS mutation in lung adenocarcinoma.
abstract: 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.
authors.affiliation: 1] Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan [2] Oncology Center, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sunaga
authors.affiliation: 1] Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan [2] Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaira
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Nishigunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-8511, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tomizawa
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Nishigunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-8511, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Surgery, National Hospital Organization Nishigunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-8511, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kakegawa
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtaki
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kasahara
authors.affiliation: Department of Thoracic Surgery, National Hospital Organization Nishigunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-8511, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Kawashima
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hisada
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Nishigunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-8511, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma371-8511, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D016209:Interleukin-8; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins