title: Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical implications and functional analysis.
abstract: Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been explored to improve the prognosis of this disease. One of these, the 47-kDa heat shock protein (HSP47), has been screened as a potential biomarker by genomic profiling and is known to be overexpressed in some malignant diseases. In this study, we explored the role and evaluated the prognostic value of HSP47 expression in ESCC. The function of this protein was analyzed by assaying proliferation, wound healing, and colony formation in an HSP47-knockdown ESCC line. The prognostic implication of HSP47 expression was analyzed by immunohistochemical staining in 157 surgical specimens. HSP47 expression level and other clinical variables were analyzed using multivariate Cox proportional hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell proliferation and colony formation. HSP47 was highly expressed in ESCC tissue samples, compared with normal esophageal tissues. The level of immunohistochemical staining of HSP47 and pathologic stage were significantly correlated with overall and recurrence-free survival, as shown by multivariate analysis (P = 0.014 and 0.044, respectively). We found that overexpression of HSP47 is associated with poor prognosis in patients with ESCC and that this is consistent with the function of HSP47 in terms of increased cell proliferation and colony formation. These results suggest that HSP47 is a potential prognostic biomarker for ESCC and merits further research for novel diagnostic and therapeutic applications.
authors.affiliation: Department of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: H W
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Translational Research, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: M C
authors.initials: MC
authors.lastname: Kang
authors.affiliation: Korea Institute of Science and Technology Information, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: M-K
authors.initials: MK
authors.lastname: Noh
authors.affiliation: Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Koh
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea. jhpark@kcch.re.kr.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000502:physiology; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D050958:HSP47 Heat-Shock Proteins; C494660:SERPINH1 protein, human
keywords: esophageal squamous cell carcinoma; heat shock protein 47; prognostic factor