Preoperative evaluation of heat shock protein 47 expression to identify patients with colorectal cancer with lymph node metastasis and poor prognosis.

Abstract

546 Background: Accumulating evidences reveal that overexpression of Heat shock protein 47 (HSP47) increase cancer progression, and that HSP47 expression in the tumor-associated stroma serve as diagnostic marker in various cancers. In addition, we recently performed immunohistochemistry to evaluate HSP47 expression in surgical colorectal cancer (CRC) specimens, and showed that the count of HSP47 positive spindle cell in cancer stroma was significantly associated with lymph node (LN) metastasis, early recurrence and poor prognosis in CRC patients. Thus, evaluating HSP47 expression in CRCs preoperatively may be valuable for planning the treatment of patients with CRC. In this study, we quantified the messenger RNA(mRNA) expression of HSP47 in CRCs by using preoperative biopsy samples, and analyzed the association between HSP47 mRNA expression and clinico-pathological factors including prognosis in patients with CRC. Methods: A total of 139 CRC samples, which were taken by biopsy before surgery at Mie University Hospital from 2000 to 2005, were enrolled. HSP47 gene expression was determined by quantitative real-time reverse transcription–PCR using Power SYBR Green PCR methods. Results: All CRC patients were classified according to the tumor-node-metastasis (TNM) classification system as follows: stage I (n = 33); stage II (n = 44); stage III (n = 33), and stage IV (n = 29). High HSP47 expression in CRC was significantly associated with higher T stage (p = 0.0163), LN metastasis (p = 0.0186), vessel invasion (p = 0.0328) and higher TNM staging (p = 0.0115). Kaplan-Meier analysis showed that patients with high HSP47 expression had significantly poorer overall survival (OS) than those with low (p = 0.0003). Furthermore, multivariate analyses revealed that HSP47 expression was an independent predictive marker for LN metastasis and poor OS in CRC patients, respectively (LN metastasis; OR; 2.3946, p = 0.0249, OS; HR; 2.7407, p = 0.00224). Conclusions: In conclusion, quantification of HSP47 expression using biopsy samples can identify the CRC patients who may suffer from LN metastasis and poor prognosis, preoperatively.