Dataset Information

Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.

ABSTRACT: 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 (Hsp90?) 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 Hsp90? 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 Hsp90? was evaluated by the calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). ROC curve showed plasma Hsp90? 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 Hsp90? exhibited a significantly higher diagnostic performance (sensitivity 93.3% vs 61.1%) in discriminating hepatocellular carcinoma (HCC) from the control. Furthermore, plasma Hsp90? 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 Hsp90? 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 Hsp90? 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.

SUBMITTER: Fu Y

PROVIDER: S-EPMC5652007 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.

Fu Yan Y Xu Xiao X Huang Dongsheng D Cui Dawei D Liu Lisheng L Liu Junwei J He Zenglei Z Liu Jingjing J Zheng Shusen S Luo Yongzhang Y

EBioMedicine 20170912

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, whic ...[more]

PMID: 28939487

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Project description:BackgroundFocal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers.ObjectiveTo ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them.MethodsA multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated.ResultsOut of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis.ConclusionThis large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

Project description:Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. The lack of effective biomarkers for the early detection of HCC results in unsatisfactory curative treatments. Here, metabolite biomarkers were identified and validated for HCC diagnosis. A total of 1,448 subjects, including healthy controls and patients with chronic hepatitis B virus infection, liver cirrhosis, and HCC, were recruited from multiple centers in China. Liquid chromatography-mass spectrometry-based metabolomics methods were used to characterize the subjects' serum metabolic profiles and to screen and validate the HCC biomarkers. A serum metabolite biomarker panel including phenylalanyl-tryptophan and glycocholate was defined. This panel had a higher diagnostic performance than did α-fetoprotein (AFP) in differentiating HCC from a high-risk population of cirrhosis, such as an area under the receiver-operating characteristic curve of 0.930, 0.892, and 0.807 for the panel versus 0.657, 0.725, and 0.650 for AFP in the discovery set, test set, and cohort 1 of the validation set, respectively. In the nested case-control study, this panel had high sensitivity (range 80.0%-70.3%) to detect preclinical HCC, and its combination with AFP provided better risk prediction of preclinical HCC before clinical diagnosis. Besides, this panel showed a larger area under the receiver-operating characteristic curve than did AFP (0.866 versus 0.682) to distinguish small HCC, and 80.6% of the AFP false-negative patients with HCC were correctly diagnosed using this panel in the test set, which was corroborated by the validation set. The specificity and biological relevance of the identified biomarkers were further evaluated using sera from another two cancers and HCC tissue specimens, respectively. Conclusion: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of HCC from at-risk populations. (Hepatology 2018;67:662-675).

Dataset Information

Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.

Publications

Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.

Similar Datasets

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