title: Identification of serum inflammatory markers as classifiers of lung cancer mortality for stage I adenocarcinoma.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. LDCT has resulted in increased detection of stage I lung cancer for which the current standard of care is surgery alone. However, approximately 30% of these patients develop recurrence and therefore are in need of further treatment upon diagnosis. This study aims to explore blood-based inflammatory biomarkers to identify patients at high-risk of mortality for which additional treatment modalities can be offered at time of diagnosis.
  
  
  METHODS
  Recent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival for lung cancer patients. To reflect the broader role of inflammation in lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of 129 lung cancer patients selected from the National Cancer Institute-Maryland case-control study. To reduce heterogeneity, we specifically focused our study on stage I lung adenocarcinoma patients.
  
  
  RESULTS
  We replicated the previous observations that IL-6 is associated with prognosis of lung cancer and extended its utility to prognosis in this highly-selected population of stage I lung adenocarcinoma patients. In addition, we developed a multi-marker, combined prognostic classifier that includes the pro-inflammatory Th-17 cell effector cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels (P for trend <0.0001). Patients in the high risk group, with high levels of both proteins had a 5-year survival rate of 46% in comparison to 93% for those with low levels of both markers. Furthermore, we validated the same trends for the IL-6 and IL-17A prognostic signature in an independent data set.
  
  
  CONCLUSIONS
  The results identified here justify further investigation of this novel, combined cytokine prognostic classifier for the identification of high-risk stage I lung adenocarcinoma patients. This classifier has the much-needed potential to identify patients at high risk of recurrence and thus prospectively identify the subset of patients requiring more aggressive treatment regimens at the time of diagnosis.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Meaney
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Zingone
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Brown
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Yunkai
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Bríd M
authors.initials: BM
authors.lastname: Ryan
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000145:classification* / Q000473:pathology; D008175:Lung Neoplasms / Q000145:classification* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor
keywords: IL-6; biomarkers; inflammation; lung cancer; survival