Plasma Levels of Heat Shock Protein 90 Alpha Associated with Lung Cancer Development and Treatment Responses
Open Access
- 30 November 2014
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 20 (23), 6016-6022
- https://doi.org/10.1158/1078-0432.ccr-14-0174
Abstract
Purpose: Altered expression of heat shock protein 90 alpha (Hsp90α) was associated with tumor development, progression, and metastasis. This study explored plasma levels of Hsp90α protein in patients with lung cancer and other controls to assess its diagnostic value and monitor treatment responses for patients with lung cancer. Experimental Design: A total of 2,247 individuals were recruited and assigned into two cohorts as static and dynamic groups. ELISA analysis and confirmation of plasma Hsp90α protein levels for association with tumor stages and treatment responses, respectively, were performed. Results: The average plasma levels of Hsp90α protein in patients with lung cancer were significantly higher than in healthy controls (P < 0.0001). Plasma levels of Hsp90α protein in patients with advanced lung cancer (stage III–IV) were higher than in patients with early-stage lung cancer (stage I–II; P < 0.001). Using a cutoff value of 56.33 ng/mL to separate lung cancer from other controls, the sensitivity and specificity reached 72.18% (95% CI, 0.695–0.749) and 78.70% (95% CI, 0.761–0.813), respectively. To confirm the different levels in the second cohort, plasma levels of Hsp90α protein showed a statistically significant difference between preoperative and postoperative patients in surgical patient groups (P < 0.007). There was also a statistically significant difference between the disease progressive group and stable disease group, with regard to partial response after chemotherapy (P < 0.0001). Conclusions: This study demonstrated that plasma Hsp90α protein levels are useful as a diagnostic biomarker in lung cancer and predict the responses of patients with lung cancer to chemotherapy. Clin Cancer Res; 20(23); 6016–22. ©2014 AACR.Keywords
This publication has 21 references indexed in Scilit:
- Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trialThe Lancet Oncology, 2013
- Cancer statistics, 2013CA: A Cancer Journal for Clinicians, 2013
- Down-regulation of cellular FLICE-inhibitory protein (Long Form) contributes to apoptosis induced by Hsp90 inhibition in human lung cancer cellsCancer Cell International, 2012
- A potentially common peptide target in secreted heat shock protein-90α for hypoxia-inducible factor-1α–positive tumorsMolecular Biology of the Cell, 2012
- Extracellular Heat Shock Protein (Hsp)70 and Hsp90α Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and InvasionPLOS ONE, 2011
- Unlocking Biomarker Discovery: Large Scale Application of Aptamer Proteomic Technology for Early Detection of Lung CancerPLOS ONE, 2010
- The Regulatory Mechanism of Extracellular Hsp90α on Matrix Metalloproteinase-2 Processing and Tumor AngiogenesisPublished by Elsevier BV ,2010
- The regulatory mechanism of Hsp90α secretion and its function in tumor malignancyProceedings of the National Academy of Sciences of the United States of America, 2009
- IP6K2 is a client for HSP90 and a target for cancer therapeutics developmentProceedings of the National Academy of Sciences of the United States of America, 2008
- Extracellular heat shock protein-90α: linking hypoxia to skin cell motility and wound healingThe EMBO Journal, 2007