title: CHIP involves in non-small cell lung cancer prognosis through VEGF pathway.
abstract: OBJECTIVE
  CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase playing vital roles in various cancers. The VEGF pathway has become an important therapeutic target in non-small cell lung cancer (NSCLC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in NSCLC. In this study we aimed to investigate the clinical function of CHIP in NSCLC and explore the relevant regulatory mechanism.
  
  
  METHODS
  QRT-PCR was performed to detect CHIP expression in NSCLC tissues. The association of CHIP expression and clinical parameters was analyzed using the Chi-square test. Kaplan- Meier and Cox analyses were performed to identify the role of CHIP in the prognosis of NSCLC patients. ELISA test was used to detect the VEGF secretion of NSCLC cells and western blot were used to detected the protein expression of VEGFR2 in NSCLC cells.
  
  
  RESULTS
  and the results revealed that CHIP expression was decreased in NSCLC tissues and significantly correlated with clinical stages, lymph node metastasis and distant metastasis (P<0.05). Moreover, Kaplan-Meier and Cox regression analyses showed that patients with negative expression of CHIP had a shorter survival time and CHIP could be an independent prognostic biomarker. In addition, ELISA tests showed that CHIP negatively regulated the secretion level of VEGF. Furthermore, western blot assay indicated that the VEGFR2 protein level was reduced after CHIP over-expression.
  
  
  CONCLUSIONS
  Taken together, our findings demonstrate for the first time that CHIP may serve as a promising prognostic biomarker for NSCLC patients and it may be involved in NSCLC angiogenesis through regulating VEGF secretion and expression of VEGFR2.
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China. Electronic address: ghehv588@yeah.net.
authors.forename: Qian
authors.initials: Q
authors.lastname: Tingting
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Jiao
authors.affiliation: College of Grain Science and Technology, Shenyang Normal University, Shenyang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Qingfeng
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yancheng
authors.affiliation: Chuzhou University, School of Biology and Food Engineering, Chuzhou, Anhui 239000, PR China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Shijun
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhaoqi
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
authors.forename: Sun
authors.initials: S
authors.lastname: Dongmei
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: ShiLong
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: CHIP; NSCLC; Prognosis; VEGF-VEGFR2