title: Identification and verification of transgelin-2 as a potential biomarker of tumor-derived lung-cancer endothelial cells by comparative proteomics.
abstract: To investigate heterogeneity of endothelial cells (ECs) in the tumor microenvironment and biomarkers for antitumor angiogenesis therapy, high-purity (>98%) normal (NECs) and tumor-derived CD105(+) ECs (TECs) were purified from a mouse Lewis lung carcinoma model bearing 0.5 cm tumors by immunomagnetic separation. Proteomics analysis revealed that 48 proteins (28 upregulated and 20 downregulated) were differentially regulated by at least 1.5-fold in TECs, and that these proteins were involved in metabolism, energy pathways, protein folding, cell growth and/or functioned as structural constituents of the cytoskeleton. Upregulation of heat shock protein 60 (Hspd1) and transgelin-2 (Tagln2) was revealed in TECs, and by immunohistochemistry (IHC) in paired tissues from 30 consecutive lung cancer (LC) patients. Higher expression levels of Hspd1, Tagln2 were detected in microvascular ECs of paratumor and tumor tissues than in paired normal counterparts. Stronger Tagln2 staining was associated with clinical stage, tumor size, and histological neural invasion. Higher Hspd1 (area under the curve [AUC], 0.82) and lower Tagln2 (AUC, 0.90) levels were detected in LC patient sera. Pearson correlation analysis revealed a positive correlation between serum Hspd1 and Tagln2 levels. In conclusion, higher Tagln2 levels were associated with tumor development, lymph node metastasis, and neural invasion in LC and may thus serve as a potential biomarker of tumor angiogenesis.
  
  
  CONCLUSIONS
  High-purity endothelial cells (normal and tumor derived) were prepared to characterize ECs heterogeneity in the tumor microenvironment and to explore biomarkers of early stages of tumor development by proteomics. Candidate proteins Hspd1 and Tagln2, were further verification in the sera and tumor tissues of lung cancer patients. Moreover, higher Tagln2 was significantly associated with clinical tumor development, metastasis, and neural invasion. All these results indicated a crucial role for Tagln2 in TECs for tumor development and metastasis.
authors.affiliation: Xiamen Center of Clinical Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.affiliation: Respiratory Department, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Hospital Infection Control Office, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Fu
authors.affiliation: Respiratory Department, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lyu
authors.affiliation: State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Peng
authors.affiliation: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Central Laboratory, Xiamen Women's and Children's Hospital, Xiamen, Fujian 361004, China. Electronic address: biozone@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Xiamen Medical College, Xiamen, Fujian 361004, China. Electronic address: lzluo@xmu.edu.cn.
authors.forename: Lianzhong
authors.initials: L
authors.lastname: Luo
authors.affiliation: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China. Electronic address: zhuohuiqin@xmu.edu.cn.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; C585385:Tagln2 protein, mouse
keywords: Biomarkers; Hspd1; Lung cancer; Microvascular endothelial cells; Tagln2