Abstract

Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.

Highlights

  • Haptoglobin (Hp) is a secreted acute phase protein that is mainly produced in liver[1]

  • Tissue Hp protein expression level is correlated with hepatocellular carcinoma (HCC) cancer differentiation in Changhua Christian Hospital (CCH) HCC patients

  • These results indicated that in HCC patients, tissue Hp protein expression levels are reduced in tumor

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Summary

Introduction

Haptoglobin (Hp) is a secreted acute phase protein that is mainly produced in liver[1]. Previous study reported the serum Hp could be regarded as an independent prognostic factor for epithelial ovarian cancer patients since patients with higher serum levels of Hp had significantly poor survival rates[7]. Sun et al demonstrated that serum Hp is highly expressed in colorectal cancer and is correlated with poor survival rate[8]. It has been shown that the increased serum levels of Hp in non-small cell lung cancer (NSCLC) is associated with advanced TNM stages and distant metastasis[9]. These findings suggest the potential role of Hp in cancer prognosis and biomarker, which is worth and clinically urgent for further investigations

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