PMID- 22298307 OWN - NLM STAT- MEDLINE DCOM- 20121011 LR - 20211021 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 11 IP - 6 DP - 2012 Jun TI - Identification of candidate biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics. PG - M111.013946 LID - 10.1074/mcp.M111.013946 [doi] LID - M111.013946 AB - To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down-regulation is involved in human bronchial epithelial carcinogenesis. FAU - Zeng, Gu-Qing AU - Zeng GQ AD - Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Zhang, Pang-Fei AU - Zhang PF FAU - Deng, Xingming AU - Deng X FAU - Yu, Feng-Lei AU - Yu FL FAU - Li, Cui AU - Li C FAU - Xu, Yan AU - Xu Y FAU - Yi, Hong AU - Yi H FAU - Li, Mao-Yu AU - Li MY FAU - Hu, Rong AU - Hu R FAU - Zuo, Jian-Hong AU - Zuo JH FAU - Li, Xin-Hui AU - Li XH FAU - Wan, Xun-Xun AU - Wan XX FAU - Qu, Jia-Quan AU - Qu JQ FAU - He, Qiu-Yan AU - He QY FAU - Li, Jian-Huang AU - Li JH FAU - Ye, Xu AU - Ye X FAU - Chen, Yu AU - Chen Y FAU - Li, Jiao-Yang AU - Li JY FAU - Xiao, Zhi-Qiang AU - Xiao ZQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120131 PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 RN - 0 (Biomarkers, Tumor) RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (HSPB1 protein, human) RN - 0 (Heat-Shock Proteins) RN - 0 (Molecular Chaperones) RN - EC 2.5.1.18 (GSTP1 protein, human) RN - EC 2.5.1.18 (Glutathione S-Transferase pi) RN - EC 2.7.3.2 (Creatine Kinase, BB Form) SB - IM MH - Amino Acid Sequence MH - Biomarkers, Tumor/chemistry/genetics/*metabolism MH - Bronchi/pathology MH - Cell Line MH - Cell Transformation, Neoplastic/chemically induced/metabolism MH - Cluster Analysis MH - Creatine Kinase, BB Form/chemistry/genetics/metabolism MH - *Early Detection of Cancer MH - Epithelial Cells/metabolism/pathology MH - Gene Expression MH - Glutathione S-Transferase pi/chemistry/genetics/metabolism MH - HSP27 Heat-Shock Proteins/chemistry/genetics/metabolism MH - Heat-Shock Proteins MH - Humans MH - Laser Capture Microdissection MH - Lung Neoplasms/diagnosis/*metabolism MH - Molecular Chaperones MH - Molecular Sequence Data MH - Neoplasms, Squamous Cell/diagnosis/*metabolism MH - Proteomics MH - ROC Curve MH - Statistics, Nonparametric MH - Tandem Mass Spectrometry PMC - PMC3433890 EDAT- 2012/02/03 06:00 MHDA- 2012/10/12 06:00 PMCR- 2013/06/01 CRDT- 2012/02/03 06:00 PHST- 2012/02/03 06:00 [entrez] PHST- 2012/02/03 06:00 [pubmed] PHST- 2012/10/12 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - S1535-9476(20)30417-5 [pii] AID - M111.013946 [pii] AID - 10.1074/mcp.M111.013946 [doi] PST - ppublish SO - Mol Cell Proteomics. 2012 Jun;11(6):M111.013946. doi: 10.1074/mcp.M111.013946. Epub 2012 Jan 31.