TY - JOUR
T1 - Aberrant expression of proteins involved in signal transduction and DNA repair pathways in lung cancer and their association with clinical parameters
AU - He, Yong
AU - Zhou, Zhen
AU - Hofstetter, Wayne L.
AU - Zhou, Yanbin
AU - Hu, Wenxian
AU - Guo, Chengcheng
AU - Wang, Li
AU - Guo, Wei
AU - Pataer, Apar
AU - Correa, Arlene M.
AU - Lu, Yiling
AU - Wang, Jing
AU - Diao, Lixia
AU - Byers, Lauren Averett
AU - Wistuba, Ignacio I.
AU - Roth, Jack A.
AU - Swisher, Stephen G.
AU - Heymach, John V.
AU - Fang, Bingliang
PY - 2012
Y1 - 2012
N2 - Background: Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues. Methodology/ Principal Findings: We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery. Conclusions/ Significance: Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers.
AB - Background: Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues. Methodology/ Principal Findings: We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery. Conclusions/ Significance: Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers.
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U2 - 10.1371/journal.pone.0031087
DO - 10.1371/journal.pone.0031087
M3 - Article
C2 - 22348039
AN - SCOPUS:84863076111
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 2
M1 - e31087
ER -