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

Abstract

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.

Aspirin inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo via inducing cell cycle arrest and apoptosis

“…Many reports have indicated that clusterin could inhibit mitochondrial apoptosis by interacting with BAX (28) and activating the Akt and NF-κB pathways to promote cancer cell survival (29,30). In a recent study, clusterin expression in nontumor liver tissue was found to be an independent adverse prognostic factor for post-operative HCC patients (31). HSP 70, an evolutionarily conserved protein, is known to increase the survivability of cells under stress.…”

Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma

“…Hepatic sCLU plays an important role in the proliferation, multidrug resistance, invasion and metastasis of HCC cells[ 63 , 64 ]. sCLU mediated the expression of MMP-2, p-AKT and E-cadherin in HCC BEL-7402 or SMMC-7721 cell lines, and down-regulating sCLU expression can significantly reduce the invasive ability of HCC cells by the selective COX-2 inhibitor meloxicam plus specific sCLU-shRNA plasmids[ 65 , 66 ]. These data indicated that sCLU is a new effective target for the occurrence, invasion and metastasis of HCC, and should have a bright future in HCC immunotherapy.…”

Head and Neck Squamous Cell Carcinoma Subtypes Based on Immunologic and Hallmark Gene Sets in Tumor and Non-tumor Tissues

“…Li et al identified five ferroptosis-related genes and established a model to predict the prognosis of patients with HNSCC (7). Nevertheless, non-tumor tissue also has a significant impact on the prognosis of tumors (8)(9)(10)(11).…”