Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis DOI Open Access
Alessandro Rizzo, Riccardo Carloni, Angela Dalia Ricci

et al.

Journal of Personalized Medicine, Journal Year: 2022, Volume and Issue: 12(8), P. 1247 - 1247

Published: July 29, 2022

Recent years have witnessed the advent of molecular profiling for intrahepatic cholangiocarcinoma (iCCA), and new techniques led to identification several alterations. Precision oncology approaches been widely evaluated are currently under assessment, as shown by recent development a wide range agents targeting Fibroblast Growth Factor Receptor (FGFR) 2, Isocitrate Dehydrogenase 1 (IDH-1), BRAF. However, knowledge gaps persist in understanding genomic landscape this hepatobiliary malignancy.In current study, we aimed comprehensively analyze clinicopathological features BAP1-mutated iCCA patients public datasets increase on biological profile iCCA.The database including 772 iCCAs, identified BAP1 mutations 120 cases (15.7%). According our analysis, no differences terms overall survival relapse-free were observed between wild-type receiving radical surgery. In addition, IDH1, PBRM1, ARID1A most commonly co-altered genes iCCAs.The characterization is destined become increasingly important, more efforts implement genomics analysis warranted.

Language: Английский

FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions DOI

Masuko Katoh,

Yohann Loriot,

Giovanni Brandi

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(4), P. 312 - 329

Published: Feb. 29, 2024

Language: Английский

Citations

63
Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD DOI Creative Commons
Yang Long,

Kunwei Niu,

Jianlin Wang

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: April 1, 2024

Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack detailed understanding oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. role protein lactylation, newly unraveled post-translational modification that orchestrates expression, remains largely elusive in pathogenesis iCCA.

Language: Английский

Citations

34
Mapping the landscape of biliary tract cancer in Europe: challenges and controversies DOI Creative Commons
Lorenza Rimassa, Shahid A. Khan, Bas Groot Koerkamp

et al.

The Lancet Regional Health - Europe, Journal Year: 2025, Volume and Issue: 50, P. 101171 - 101171

Published: Feb. 19, 2025

Biliary tract cancer (BTC) is becoming more common worldwide, with geographic differences in incidence and risk factors. In Europe, BTC may be associated primary sclerosing cholangitis, lithiasis, liver cirrhosis, but frequently observed as a sporadic disease. increasingly affects patients under 60 years, resulting significant social economic burden. Early diagnosis remains challenging due to vague symptoms 50% of BTC, lack specific biomarkers, late presentation poor prognosis. The identification at increased reliable biomarkers require collaborative efforts make faster progress. This Series paper highlights the disparities access diagnostic tools multidisciplinary care particularly economically disadvantaged regions, while identifying priority areas for improvement. Addressing these inequities requires harmonised guidelines, accelerated pathways curative treatments, improved awareness among healthcare professionals public. Multidisciplinary teams (MDTs) are crucial improving patient outcomes, yet inconsistencies exist their implementation not only between different countries, also centres within country. Collaboration standardisation treatment protocols across Europe essential effectively address management BTC.

Language: Английский

Citations

1
DNA methylation-based classifier differentiates intrahepatic pancreato-biliary tumours DOI Creative Commons
Mihnea P. Dragomir, Teodor G. Calina, Eilís Pérez

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104657 - 104657

Published: June 21, 2023

Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task.We assembled genome-wide methylation data for iCCA (n = 259), PAAD 431), normal bile duct 70) publicly available sources. split cohort into a reference 399) validation set 361). Using the cohort, we trained three machine learning models to differentiate between these entities. Furthermore, validated classifiers on technical used an internal 72) test our classifier.On neural network, support vector machine, random forest reached accuracies 97.68%, 95.62%, 96.5%, respectively. Filtering by anomaly detection thresholds improved accuracy 99.07% (37 samples excluded filtering), 96.22% (17 excluded), 100% (44 excluded) forest, Because best balance number predictable cases tested network with applied filters in-house obtaining 95.45%.We developed classifier can iCCAs, PAAD, tissue high accuracy. This tool be improving diagnosis pancreato-biliary cancers liver.This work was supported Berlin Institute Health (JCS Program), DKTK (Young Investigator Grant 2022), German Research Foundation (493697503 314905040 - SFB/TRR 209 Liver Cancer B01), Aid (70113922).

Language: Английский

Citations

17
Proteogenomic characterization of cholangiocarcinoma DOI Creative Commons

Mengjie Deng,

Peng Ran,

Lingli Chen

et al.

Hepatology, Journal Year: 2022, Volume and Issue: 77(2), P. 411 - 429

Published: June 18, 2022

Background and Aims: Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding few effective therapeutic approaches. We aimed at providing proteogenomic CCA characterization to inform biological processes treatment vulnerabilities. Approach Results: Integrative genomic analysis functional validation uncovered perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, FGFR2 fusions in CCA. Proteomic clustering identified three subtypes distinct clinical outcomes, molecular features, potential therapeutics. Phosphoproteomics characterized targetable kinases CCA, suggesting strategies for CDK MAPK inhibitors. Patients HBV infection showed increased antigen processing presentation (APC) T cell infiltration, conferring favorable prognosis compared those without infection. The extrahepatic recommended the feasible application vascular endothelial‐derived growth factor Multiomics profiling presented distinctive characteristics large bile duct small intrahepatic immune landscape further revealed diverse tumor microenvironments, C1 C5 might benefit from checkpoint therapy. TCN1 was as prognostic biomarker, promoting by enhancing vitamin B12 metabolism. Conclusions: 217 CCAs 197 paired normal adjacent tissues their targets. multiomics analyses other databases some validations have indicated regarding clinical, biological, approaches management

Language: Английский

Citations

28
Integrative multiomics enhancer activity profiling identifies therapeutic vulnerabilities in cholangiocarcinoma of different etiologies DOI
Jing Han Hong, Chern Han Yong,

Hong Lee Heng

et al.

Gut, Journal Year: 2023, Volume and Issue: 73(6), P. 966 - 984

Published: Nov. 24, 2023

Objectives Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, an urgent clinical need for new therapies. Knowledge of the CCA epigenome largely limited to aberrant DNA methylation. Dysregulation enhancer activities has been identified affect carcinogenesis leveraged therapies but uninvestigated in CCA. Our aim identify potential therapeutic targets different subtypes through profiling. Design Integrative multiomics activity profiling diverse was performed. A panel cell lines, patient-derived line-derived xenografts were used study enriched pathways vulnerabilities. NanoString, multiplex immunohistochemistry staining single-cell spatial transcriptomics explore immunogenicity Results We three distinct groups, associated etiologies unique pathways. Drug inhibitors reduced tumour growth vitro vivo models. The first group (ESTRO), mostly fluke-positive CCAs, displayed activation estrogen signalling sensitive MTOR inhibitors. Another (OXPHO), BAP1 IDH -mutant activated oxidative phosphorylation pathways, Immune-related final (IMMUN), made up immunogenic subtype aristolochic acid (AA) mutational signatures. Intratumour differences AA mutation load correlated intratumour variation immune populations. Conclusion elucidates mechanisms underlying dysregulation deepens understanding tumourigenesis processes subtypes, significant therapeutics benefits.

Language: Английский

Citations

13
Biological Roles and Clinical Applications of Exosomes in Breast Cancer: A Brief Review DOI Open Access
Han Wang, Ruo Wang, Kunwei Shen

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4620 - 4620

Published: April 24, 2024

Breast cancer (BC) is a global health risk for women and has high prevalence rate. The drug resistance, recurrence, metastasis of BC affect patient prognosis, thus posing challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells; they have double-layered lipid membrane structure contain rich biological information. They mediate intercellular communication pivotal roles in tumor development, progression, resistance. important cell mediators the microenvironment (TME). utilized as diagnostic prognostic biomarkers estimating treatment efficacy potential function tools enable targeted delivery antitumor drugs. This review introduces recent progress research on how exosomes influence development TME. We also present application tools.

Language: Английский

Citations

4
Single‐Cell Transcriptomic Analysis Reveals an Aggressive Basal‐Like Tumor Cell Subpopulation Associated With Poor Prognosis in Intrahepatic Cholangiocarcinoma DOI

Changyi Liao,

Yuting Zhang, Jing Yang

et al.

Journal of Gastroenterology and Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

ABSTRACT Background and Aim Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer whose incidence increasing globally. However, high tumor heterogeneity of ICC restricts efficacy available systematic therapies. We aim to dissect utilizing high‐resolution single‐cell RNA sequencing identify novel therapeutic targets. Methods performed (scRNA‐seq) 26 samples from 23 patients spatial transcriptomic six sections patients. Bulk RNA‐seq data two public datasets were used for validation. Additionally, immunohistochemical staining multiplex immunofluorescence conducted validate infiltration distribution cells in microenvironment. Results discovered that malignant exhibited a remarkably degree heterogeneity. identified basal‐like cell subpopulation characterized by expression basal epithelial related genes including KRT5, KRT6A, KRT17. The was activation MET signaling extracellular matrix organization associated with invasion correlated poor prognosis. Cell–cell communication analysis further showed significant HGF‐MET interaction between inflammatory cancer–associated fibroblasts (iCAFs) cells. found iCAFs major source HGF environment contributed phenotype formation axis. Conclusions an aggressive subpopulation, which prognosis ICC. pathway contributes aggressiveness serves as target

Language: Английский

Citations

0
Molecular signatures of intrahepatic Cholangiocarcinoma: Role in targeted therapy selection DOI

Tetiana Glushko,

James Costello,

Ranjit S. Chima

et al.

European Journal of Radiology, Journal Year: 2025, Volume and Issue: unknown, P. 112056 - 112056

Published: March 1, 2025

Language: Английский

Citations

0
Genetic predictors of postoperative recurrence in node-negative intrahepatic cholangiocarcinoma DOI

Bo Zhang,

Xiang‐Yu Wang,

Luyu Yang

et al.

Updates in Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0