Clusterin expression in nontumor tissue in patients with resectable hepatocellular carcinoma related with postresectional survival.

BACKGROUND Surgical resection offers an effective treatment for patients with hepatocellular carcinoma (HCC); however, it has high tumor recurrence rate. Clusterin is a highly conserved glycoprotein that enhances cell aggregation in vitro. It is upregulated in several types of cancers such as breast, ovarian, colon, prostate and kidney cancers, and HCC. Clusterin overexpression is correlated with tumor metastasis. We evaluated the significance of clusterin expression levels in serum and resected tissues of patients with HCC. METHODS Serum, resected tumor tissue, and nontumor tissue were collected from 140 patients with HCC undergoing hepatic resection. Serum clusterin levels were determined by enzyme-linked immunosorbent assay. Clusterin expression in resected tissue was evaluated by immunohistochemistry. Median follow-up time was 57.8 months. RESULTS Mean serum clusterin levels were found to be 130.0 ± 58.7 µg/mL (range, 10.1-366.6 µg/mL). Serum clusterin levels were independent of tumor stage and deterioration of liver function in patients. No significant difference was observed in the survival of patients with high (>130.0 ± 58.7 µg/mL) or low (≤130.0 ± 58.7 µg/mL) serum clusterin level. Clusterin was expressed in HCC tissues of 76 patients (54.3%) and nontumor liver tissues of 53 patients (37.9%). No significant difference was observed in the survival of patients with positive or negative clusterin expression in HCC tissues. In nontumor tissues, patients with positive clusterin expression were observed to have low postoperative disease-free survival rate (p = 0.001) compared to patients with negative clusterin expression. Multivariate analysis showed that tumor with macrovascular/microvascular invasion and clusterin expression in nontumor tissues are independent prognostic factors following hepatic resection. CONCLUSION In HCC, clusterin expression in nontumor tissue shows worse prognosis after hepatic resection. Clusterin can be a prognostic marker for patients with postresection HCC.

[1]  Heba F Pasha,et al.  Clinical significance of serum clusterin as a biomarker for evaluating diagnosis and metastasis potential of viral-related hepatocellular carcinoma. , 2012, Clinical biochemistry.

[2]  D. Xie,et al.  Clusterin plays an important role in hepatocellular carcinoma metastasis , 2006, Oncogene.

[3]  Yan Fang,et al.  Up‐regulated expression of cytoplasmic clusterin in human ovarian carcinoma , 2005, Cancer.

[4]  W. Kim,et al.  Overexpression of clusterin in human hepatocellular carcinoma. , 2004, Human pathology.

[5]  L. French,et al.  Myc-transformed epithelial cells down-regulate clusterin, which inhibits their growth in vitro and carcinogenesis in vivo. , 2004, Cancer research.

[6]  G. Chau,et al.  Long-term results of hepatic resection for hepatocellular carcinoma originating from the noncirrhotic liver. , 2004, Archives of surgery.

[7]  W. Dove,et al.  Clusterin as a biomarker in murine and human intestinal neoplasia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Xiaohang Zhao,et al.  Loss of clusterin both in serum and tissue correlates with the tumorigenesis of esophageal squamous cell carcinoma via proteomics approaches. , 2003, World journal of gastroenterology.

[9]  I. Trougakos,et al.  Clusterin/apolipoprotein J in human aging and cancer. , 2002, The international journal of biochemistry & cell biology.

[10]  M. Gleave,et al.  Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential. , 2002, The Journal of urology.

[11]  C. Petito,et al.  Overexpression of clusterin in human breast carcinoma. , 2000, The American journal of pathology.

[12]  S. Fan,et al.  Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. , 2000, Annals of surgery.

[13]  A. Rademaker,et al.  Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  O. Blaschuk,et al.  Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid. , 1983, The Journal of biological chemistry.

[15]  W. Bursch,et al.  Expression of clusterin (testosterone-repressed prostate message-2) mRNA during growth and regeneration of rat liver , 2009, Archives of Toxicology.

[16]  J. Willis,et al.  Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer , 2006, Cell Death and Differentiation.

[17]  M. Scaltriti,et al.  Clusterin (SGP‐2, ApoJ) expression is downregulated in low‐ and high‐grade human prostate cancer , 2004, International journal of cancer.

[18]  G. Chau,et al.  Spectrum and significance of microscopic vascular invasion in hepatocellular carcinoma. , 2003, Surgical oncology clinics of North America.