Dataset Information

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

ABSTRACT: Liver cancer is among the top leading causes of cancer mortality worldwide. Particularly, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) have been extensively investigated from the aspect of tumor biology. However, a comprehensive and systematic understanding of the molecular characteristics of HCC and CCA remains absent. Here, we characterized the proteome landscapes of HCC and CCA using the data-independent acquisition (DIA) mass spectrometry (MS) method. By comparing the quantitative proteomes of HCC and CCA, we found several differences between the two cancer types. In particular, we found an abnormal lipid metabolism in HCC and activated extracellular matrix-related pathways in CCA. We next developed a three-protein classifier to distinguish CCA from HCC, achieving an area under the curve (AUC) of 0.92, and an accuracy of 90% in an independent validation cohort of 51 patients. The distinct molecular characteristics of HCC and CCA presented in this study provide new insights into the tumor biology of these two major important primary liver cancers. Our findings may help develop more efficient diagnosis protocols and new targeted drug treatments.

ORGANISM(S): Homo Sapiens

SUBMITTER: Tiannan Guo

PROVIDER: PXD043265 | iProX | Wed Jun 21 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Publications

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Yi Xiao X Zhu Jiang J Liu Wei W Peng Li L Lu Cong C Sun Ping P Huang Lingling L Nie Xiu X Huang Shi'ang S Guo Tiannan T Zhu Yi Y

Molecular & cellular proteomics : MCP 20230622 8

Liver cancer is among the top leading causes of cancer mortality worldwide. Particularly, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) have been extensively investigated from the aspect of tumor biology. However, a comprehensive and systematic understanding of the molecular characteristics of HCC and CCA remains absent. Here, we characterized the proteome landscapes of HCC and CCA using the data-independent acquisition (DIA) mass spectrometry (MS) method. By comparing ...[more]

PMID: 37353004

Similar Datasets

Project description:The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by mapping the entire liver of patients with HCC. We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes with intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center in individual livers of 11 patients with HCC and on selected LCM samples. HBV biomarkers were determined by real-time PCR and confocal immunofluorescence. Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HBsAg. The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipid and fatty acid, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARa/RXRa nuclear receptors, comprising PGC1 and FOXO1, two key regulators of the hepatic metabolic functions and HBV transcription. These findings were confirmed by gene expression of microdissected hepatocytes. However, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen (CTA) genes, NUF2 and TTK. HCC-associated with HBV is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets. Samples were obtained at various distances from the tumor center in individual livers of 11 patients with HBV-associated HCC. Whole liver tissue samples were compared to LCM samples of malignant and non-malignant hepatocytes obtained from the same livers. This dataset is part of the TransQST collection.

Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling we demonstrated that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 non-redundant genes that significantly discriminate the tumor stroma from non tumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix and Transforming Growth Factor beta (TGFM-NM-2) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increase expression of Collagen 4, Laminin, Osteopontin/SPP1, KIAA0101 and TGFM-NM-22 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of Osteopontin, TGFM-NM-22 and Laminin in the stroma of ICC was significantly correlated with patient overall survival. More importantly, multivariate analysis demonstrated that the stromal expression of Osteopontin was an independent prognostic marker for overall and disease-free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidates biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. 20 RNA samples were analyzed, from 10 patients with ICC. For each patient, RNA were isolated from laser capture microdissected (LCM) stroma from tumor and non tumor areas.

Dataset Information

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Publications

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets