High Expression of Heat Shock Protein 90 Is Associated with Tumor Aggressiveness and Poor Prognosis in Patients with Advanced Gastric Cancer
Open Access
- 26 April 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (4), e62876
- https://doi.org/10.1371/journal.pone.0062876
Abstract
The heat shock protein 90 (HSP90) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of HSP90 in gastric cancer has not been thoroughly elucidated. The aim of this study is to investigate the relationship of HSP90 expression with clinicopathological parameters and prognosis in advanced gastric cancer, and estimate the alteration of HSP90 expression after neoadjuvant chemotherapy. HSP90 and matrix metallopeptidase 9 (MMP-9) antigen expression was evaluated by immunohistochemistry in 322 advanced gastric carcinoma samples. The relationships between HSP90 and clinicopathological parameters and prognosis were analyzed. The response of HSP90 level was assessed in chemotherapeutic effect in 54 patients received 1–2 cycles of neoadjuvant chemotherapy. The positive expression of HSP90 was found to be 69.6% in 322 advanced gastric carcinoma samples. HSP90 protein expression was significantly associated with depth invasion ( P <0.001), lymph node metastasis ( P <0.001) and stage of disease ( P <0.001). The positive rates of HSP90 expression were higher in both prominent serosal invasion group ( P <0.001) and lymph node metastasis group ( P <0.001). Moreover, HSP90 was significantly correlated with MMP-9 among 322 gastric cancer tissues ( P <0.001). In univariate and multivariate analyses, HSP90 was an independent prognostic factor for both recurrence-free survival (RFS) and overall survival (OS). These results suggested that HSP90 may play an important role on tumor invasion, metastasis and prognosis, and might act as a promising target for prognostic prediction.Keywords
This publication has 25 references indexed in Scilit:
- Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)BMC Cancer, 2011
- Matrix metalloproteinase‐9 is associated with disease‐free survival and overall survival in patients with gastric cancerInternational Journal of Cancer, 2010
- Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trialThe Lancet, 2010
- Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumoursHistopathology, 2010
- The role of heat shock proteins in gastrointestinal diseasesGut, 2009
- Integration of Gene Dosage and Gene Expression in Non-Small Cell Lung Cancer, Identification of HSP90 as Potential TargetPLOS ONE, 2008
- Inhibition of heat shock protein 90 impairs epidermal growth factor–mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivoMolecular Cancer Therapeutics, 2007
- Heat Shock Protein 70 Increases Tumorigenicity and Inhibits Apoptosis in Pancreatic AdenocarcinomaCancer Research, 2007
- Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the WorldJournal of Clinical Oncology, 2006
- Hsp90 as a therapeutic target in prostate cancerSeminars in Oncology, 2003