Abstract

BackgroundHepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease.MethodsPlasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA.ResultsThe levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902–0.938) or HSP90α (AUC 0.836, 95%CI 0.810–0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925–0.957) significantly improved the diagnostic efficiency for HCC patients.ConclusionThe results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

Highlights

  • Hepatocellular carcinoma (HCC) is a major health problem worldwide

  • A total of 901 cases in this study consisted of 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma (HH) patients and 230 healthy controls (Raw data for each cohort are atttached in Additional files 1, 2, 3 and 4)

  • Statistical analysis showed that HSP90α was at significantly higher levels in HH, SHC and HCC patient cohorts when compared to the healthy donors (HD) cohort (p < 0.001, p < 0.001, p < 0.001, respectively)

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a major health problem worldwide. the popular tumor marker, AFP, lacks sensitivity its specificity is high. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. Hepatocellular carcinoma (HCC), as the major type of primary liver cancer, is the fifth most common tumor worldwide and the third leading cause of cancer mortality, responsible for 745,500 cancer deaths annually [1]. Heat shock protein 90 (HSP90) is an evolutionarily highly conserved intracellular molecular chaperone that is usually induced in response to cellular stress. It assists (2020) 20:6 the maturation of an array of client proteins. The plasma HSP90α levels were not elevated in benign liver tumors and secondary hepatic carcinoma (SHC) patients in this study. In order to establish whether plasma HSP90α levels can be used as a biomarker for HCC in the clinic, in the current study we measured plasma HSP90α levels in HCC and SHC patients as well as benign liver tumor cohort

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