Stat3 downstream genes serve as biomarkers in human lung carcinomas and chronic obstructive pulmonary disease.
Smoking causes lung cancer and chronic obstructive pulmonary disease (COPD) that impose severe health problem to humans. Both diseases are related to each other and can be induced by chronic inflammation in the lung. To identify the molecular mechanism for lung cancer formation, a CCSP-rtTA/(teto)(7)Stat3C bitransgenic model was generated recently. In this model, persistent activation of the Stat3 signaling pathway induced pulmonary inflammation and adenocarcinoma formation in the lung. A group of Stat3 downstream genes were identified by Affymetrix GeneChip microarray analysis that can be used as biomarkers for lung cancer diagnosis and prognosis. To determine which human lung cancers are related to the Stat3 pathway, multiple Stat3 downstream genes were screened in human lung cancers (adenocarcinomas and squamous cell carcinomas) and lung tissue with COPD. In both cancer and COPD, the Stat3 gene was up-regulated. A panel of Stat3-up-regulated downstream genes in mice was up-regulated in human adenocarcinomas, but not in human squamous cell carcinomas. This panel of genes was also modestly up-regulated in lung tissue with COPD from patients with a history of smoking and not up-regulated in those without histories of smoking. Several Stat3-down-regulated downstream genes also showed differential expression patterns in carcinoma and COPD. These studies support a concept that Stat3 is a potent oncogenic molecule that plays a role in formation of lung adenocarcinomas in both mice and humans. The carcinogenesis of adenocarcinoma and squamous cell carcinoma is mediated by different molecular mechanisms and pathways in vivo. Stat3 and its downstream genes can serve as biomarkers for lung adenocarcinoma and COPD diagnosis and prognosis in mice and humans.
Qu
Peng
P
Department of Pathology and Laboratory Medicine, The Center for Immunobiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Roberts
Jennifer
J
Li
Yuan
Y
Albrecht
Marjorie
M
Cummings
Oscar W
OW
Eble
John N
JN
Du
Hong
H
Yan
Cong
C
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*
D015415:Biomarkers; D012334:RNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse