Current Advances in Basic and Translational Research of Cholangiocarcinoma

Sato, Keisaku; Baiocchi, Leonardo; Kennedy, Lindsey; Zhang, Wenjun; Ekser, Burçin; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco

doi:10.3390/cancers13133307

Cited by 7 publications

(6 citation statements)

References 115 publications

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“…1,2 Liver cancer is the second most common death-causing tumor after pancreatic cancer, and 5-year survival is still <20% because of challenging early diagnosis and limited treatment options, especially for CCA. 3 Liver cancer is heterogeneous, and in some cases, liver tumors display characteristics of both HCC and CCA, which is referred to as combined hepatocellular cholangiocarcinoma (cHCC-CCA). 4 Pathologic characteristics of cHCC-CCA are similar to those in HCC, but not CCA, although further studies are required to establish diagnostic testing and specific treatment options.…”

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confidence: 99%

The Functional Roles of Immune Cells in Primary Liver Cancer

Pham¹,

Kyritsi²,

Zhou³

et al. 2022

The American Journal of Pathology

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confidence: 99%

The Functional Roles of Immune Cells in Primary Liver Cancer

Pham¹,

Kyritsi²,

Zhou³

et al. 2022

The American Journal of Pathology

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“…A new signature matrix file is needed to be generated from scRNA-seq data of liver tissues with tumors to distinguish normal and malignant hepatic cells. In addition, PSC is a common risk factor for cholangiocarcinoma (CCA) ( 52 ), but detailed mechanisms of biliary tumorigenesis mediated by cholestatic liver injury are still undefined. Therefore, there may be novel hepatic cell phenotypes in PSC livers, such as a precursor phenotype of CCA, and our approach in this study may not be able to distinguish these phenotypes from normal cholangiocytes.…”

Section: Discussionmentioning

confidence: 99%

Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis

Pham,

Sato

2024

Front. Med.

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IntroductionPrimary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are characterized by ductular reaction, hepatic inflammation, and liver fibrosis. Hepatic cells are heterogeneous, and functional roles of different hepatic cell phenotypes are still not defined in the pathophysiology of cholangiopathies. Cell deconvolution analysis estimates cell fractions of different cell phenotypes in bulk transcriptome data, and CIBERSORTx is a powerful deconvolution method to estimate cell composition in microarray data. CIBERSORTx performs estimation based on the reference file, which is referred to as signature matrix, and allows users to create custom signature matrix to identify specific phenotypes. In the current study, we created two custom signature matrices using two single cell RNA sequencing data of hepatic cells and performed deconvolution for bulk microarray data of liver tissues including PSC and PBC patients.MethodsCustom signature matrix files were created using single-cell RNA sequencing data downloaded from GSE185477 and GSE115469. Custom signature matrices were validated for their deconvolution performance using validation data sets. Cell composition of each hepatic cell phenotype in the liver, which was identified in custom signature matrices, was calculated by CIBERSORTx and bulk RNA sequencing data of GSE159676. Deconvolution results were validated by analyzing marker expression for the cell phenotype in GSE159676 data.ResultsCIBERSORTx and custom signature matrices showed comprehensive performance in estimation of population of various hepatic cell phenotypes. We identified increased population of large cholangiocytes in PSC and PBC livers, which is in agreement with previous studies referred to as ductular reaction, supporting the effectiveness and reliability of deconvolution analysis in this study. Interestingly, we identified decreased population of small cholangiocytes, periportal hepatocytes, and interzonal hepatocytes in PSC and PBC liver tissues compared to healthy livers.DiscussionAlthough further studies are required to elucidate the roles of these hepatic cell phenotypes in cholestatic liver injury, our approach provides important implications that cell functions may differ depending on phenotypes, even in the same cell type during liver injury. Deconvolution analysis using CIBERSORTx could provide a novel approach for studies of specific hepatic cell phenotypes in liver diseases.

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“…These genes encode critical cancerassociated intermediates in several important signaling pathways [2,19,20] impacting tumor progression, aggressive behavior, and drug resistance. Whole genome sequencing implicated TP53 and KRAS to be among the most frequently mutated genes (53% and 26%, respectively) and were attributed to the poor prognosis cohort [17,21]. In addition, transcriptomic and epigenetic approaches successfully catalogued genetic variations with the pathologic spectrum of CCA subtypes.…”

Section: Introductionmentioning

confidence: 99%

SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment

Czekay,

Higgins,

Aydin

et al. 2024

Cells

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A heterogenous population of inflammatory elements, other immune and nonimmune cells and cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs are the prominent mesenchymal cell type in the tumor microenvironment (TME), where their presence and abundance signal a poor prognosis. CAFs play a major role in the progression of various cancers by remodeling the supporting stroma into a dense, fibrotic matrix while secreting factors that promote the maintenance of cancer stem-like characteristics, tumor cell survival, aggressive growth and metastasis and reduced sensitivity to chemotherapeutics. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Identifying the molecular underpinnings for such multidirectional crosstalk among the various normal and neoplastic cell types in the TME may provide new targets and novel opportunities for therapeutic intervention. This review highlights recent concepts regarding the complexity of CAF biology in cholangiocarcinoma, a highly desmoplastic cancer. The discussion focuses on CAF heterogeneity, functionality in drug resistance, contributions to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.

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Current Advances in Basic and Translational Research of Cholangiocarcinoma

Cited by 7 publications

References 115 publications

The Functional Roles of Immune Cells in Primary Liver Cancer

The Functional Roles of Immune Cells in Primary Liver Cancer

Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis

SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment

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