Dataset Information

Comprehensive proteomics characterization identify biomarkers of liver cancer subtypes

ABSTRACT: Recurrence and metastasis remain the major obstacles to prognosis of hepatocellular carcinoma (HCC), but the relationship between proteomics and poor prognosis need to be studied more systematically. In this study, we performed the proteomics data collected from 85 HCC tumors and 18 adjacent normal tissues (ANTs) to establish the proteomics profiles of HCC and reveal the correlation between poteomics and ubiquitomics features of tumor tissues in HCC. Our data bring new insights on multi-omics data and have the potential to further understand the relationship between post-translational modification (PTM) levels of proteins and different molecular and clinical features of HCC patients. XAD1—XAD18 --- HCC adjacent normal tissues XC1—XC85--- HCC tumor tissues

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Chuanming Xie

LAB HEAD: Chuanming Xie

PROVIDER: PXD047168 | Pride | 2025-04-07

REPOSITORIES: Pride

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Publications

Integrated ubiquitomics characterization of hepatocellular carcinomas.

Lin Xiao-Tong XT Luo Yuan-Deng YD Mao Cui C Gong Yi Y Hou Yu Y Zhang Lei-Da LD Gu Yong-Peng YP Wu Di D Zhang Jie J Zhang Yu-Jun YJ Tan De-Hong DH Xie Chuan-Ming CM

Hepatology (Baltimore, Md.) 20240930

<h4>Background and aims</h4>Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic ...[more]

PMID: 39348425

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Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.

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