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A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic.

ABSTRACT: A sensitive and specific diagnosis biomarker, in principle scalable to most cancer types, is needed to reduce the prevalent cancer mortality. Meanwhile, the investigation of diagnosis determinants of a biomarker will facilitate the interpretation of its screening results in clinic. Here we design a large-scale (1558 enrollments), multicenter (multiple hospitals), and cross-validation (two datasets) clinic study to validate plasma Hsp90? quantified by ELISA as a pan-cancer biomarker. ROC curve shows the optimum diagnostic cutoff is 69.19 ng/mL in discriminating various cancer patients from all controls (AUC 0.895, sensitivity 81.33% and specificity 81.65% in test cohort; AUC 0.893, sensitivity 81.72% and specificity 81.03% in validation cohort). Similar results are noted in detecting early-stage cancer patients. Plasma Hsp90? maintains also broad-spectrum for cancer subtypes, especially with 91.78% sensitivity and 91.96% specificity in patients with AFP-limited liver cancer. In addition, we demonstrate levels of plasma Hsp90? are determined by ADAM10 expression, which will affect Hsp90? content in exosomes. Furthermore, Western blotting and PRM-based quantitative proteomics identify that partial false ELISA-negative patients secret high levels of plasma Hsp90?. Mechanism analysis reveal that TGF?-PKC? gene signature defines a distinct pool of hyperphosphorylated Hsp90? at Theronine residue. In clinic, a mechanistically relevant population of false ELISA-negative patients express also higher levels of PKC?. In sum, plasma Hsp90? is a novel pan-cancer diagnosis biomarker, and cancer diagnosis with plasma Hsp90? is particularly effective in those patients with high expression of ADAM10, but may be insufficient to detect the patients with low ADAM10 and those with hyperphosphorylated Hsp90?.

SUBMITTER: Liu W

PROVIDER: S-EPMC6726694 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic.

Liu Wei W Li Jie J Zhang Ping P Hou Qiaoyun Q Feng Shi S Liu Lisheng L Cui Dawei D Shi Hubing H Fu Yan Y Luo Yongzhang Y

Cancer science 20190809 9

A sensitive and specific diagnosis biomarker, in principle scalable to most cancer types, is needed to reduce the prevalent cancer mortality. Meanwhile, the investigation of diagnosis determinants of a biomarker will facilitate the interpretation of its screening results in clinic. Here we design a large-scale (1558 enrollments), multicenter (multiple hospitals), and cross-validation (two datasets) clinic study to validate plasma Hsp90α quantified by ELISA as a pan-cancer biomarker. ROC curve sh ...[more]

PMID: 31343810

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Project description:More sensitive biomarker is urgently needed to reduce the mortality caused by the worldwide prevalent liver cancer. This study aims to assess whether quantitative measurement of heat shock protein 90alpha (Hsp90α) in plasma can improve the diagnosis accuracy and monitor treatment response of liver cancer patients. We analyzed the data from an official (registered at ClinicalTrial.gov: NCT02324127), large-scale (1647 enrollments), and multicenter (three independent hospitals) clinical trial, which quantitatively measured plasma Hsp90α by ELISA for patients with liver cancer, patients with at-risk liver diseases (including hepatitis, liver cirrhosis, focal nodular hyperplasia), and healthy individuals. Diagnostic performance of plasma Hsp90α was evaluated by the calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). ROC curve showed plasma Hsp90α can discriminating liver cancer with a sensitivity of 92.7% and specificity of 91.3% from non-liver cancer control. Similar results were noted in detecting early-stage liver cancer (sensitivity 91.4%, specificity 91.3%). In a parallel study compared with AFP20, plasma Hsp90α exhibited a significantly higher diagnostic performance (sensitivity 93.3% vs 61.1%) in discriminating hepatocellular carcinoma (HCC) from the control. Furthermore, plasma Hsp90α measurement maintained distinctly excellent diagnostic accuracy in distinguishing AFP-negative HCC patients (sensitivity 93.9%, specificity 91.3%) and AFP-limited liver cancer (sensitivity 96.6%, specificity 90.3%). In the efficacy monitoring study, levels of plasma Hsp90α were dramatically decreased after surgery (P=0.005), and correlated significantly with tumor size during interventional therapy (P≤0.05). These findings highlight that plasma Hsp90α as a biomarker for the diagnosis of liver cancer, and can be used to evaluate the therapeutic efficacy of liver cancer patients underwent surgery, or interventional therapy.

Dataset Information

A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic.

Publications

A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic.

Similar Datasets

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