Multi-Omics Classification of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jul 27

PMID 39061233

Authors

Laura Alaimo

Sara Boggio

Giovanni Catalano

Giuseppe Calderone

Edoardo Poletto

Mario De Bellis

Tommaso Campagnaro

Corrado Pedrazzani

Simone Conci

Andrea Ruzzenente

Affiliations

Soon will be listed here.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous disease characterized by a dismal prognosis. Various attempts have been made to classify ICC subtypes with varying prognoses, but a consensus has yet to be reached. This systematic review aims to gather relevant data on the multi-omics-based ICC classification. The PubMed, Embase, and Cochrane databases were searched for terms related to ICC and multi-omics analysis. Studies that identified multi-omics-derived ICC subtypes and investigated clinicopathological predictors of long-term outcomes were included. Nine studies, which included 910 patients, were considered eligible. Mean 3- and 5-year overall survival were 25.7% and 19.6%, respectively, for the multi-omics subtypes related to poor prognosis, while they were 70.2% and 63.3%, respectively, for the subtypes linked to a better prognosis. Several negative prognostic factors were identified, such as genes' expression profile promoting inflammation, mutations in the KRAS gene, advanced tumor stage, and elevated levels of oncological markers. The subtype with worse clinicopathological characteristics was associated with worse survival (Ref.: good prognosis subtype; pooled hazard ratio 2.06, 95%CI 1.67-2.53). Several attempts have been made to classify molecular ICC subtypes, but they have yielded heterogeneous results and need a clear clinical definition. More efforts are required to build a comprehensive classification system that includes both molecular and clinical characteristics before implementation in clinical practice to facilitate decision-making and select patients who may benefit the most from comprehensive molecular profiling in the disease's earlier stages.

References

. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol. 2023; 79(1):181-208. DOI: 10.1016/j.jhep.2023.03.010. View

Pavicevic S, Reichelt S, Uluk D, Lurje I, Engelmann C, Modest D . Prognostic and Predictive Molecular Markers in Cholangiocarcinoma. Cancers (Basel). 2022; 14(4). PMC: 8870611. DOI: 10.3390/cancers14041026. View

Zhu A, Macarulla T, Javle M, Kelley R, Lubner S, Adeva J . Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021; 7(11):1669-1677. PMC: 8461552. DOI: 10.1001/jamaoncol.2021.3836. View

Jing C, Fu Y, Huang J, Zhang M, Yi Y, Gan W . Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma. Oncologist. 2018; 23(12):1482-1493. PMC: 6292551. DOI: 10.1634/theoncologist.2017-0439. View

Lin J, Dai Y, Sang C, Song G, Xiang B, Zhang M . Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities. J Immunother Cancer. 2022; 10(7). PMC: 9310257. DOI: 10.1136/jitc-2022-004892. View

Ahn K, OBrien D, Kang Y, Mounajjed T, Kim Y, Kim T . Prognostic subclass of intrahepatic cholangiocarcinoma by integrative molecular-clinical analysis and potential targeted approach. Hepatol Int. 2019; 13(4):490-500. DOI: 10.1007/s12072-019-09954-3. View

Wu Y, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X . Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013; 3(6):636-47. PMC: 3694764. DOI: 10.1158/2159-8290.CD-13-0050. View

Amin M, Greene F, Edge S, Compton C, Gershenwald J, Brookland R . The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017; 67(2):93-99. DOI: 10.3322/caac.21388. View

Sapisochin G, Ivanics T, Subramanian V, Doyle M, Heimbach J, Hong J . Multidisciplinary treatment for hilar and intrahepatic cholangiocarcinoma: A review of the general principles. Int J Surg. 2020; 82S:77-81. DOI: 10.1016/j.ijsu.2020.04.067. View

10.

Andersen J, Spee B, Blechacz B, Avital I, Komuta M, Barbour A . Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology. 2011; 142(4):1021-1031.e15. PMC: 3413201. DOI: 10.1053/j.gastro.2011.12.005. View

11.

Carotenuto M, Sacco A, Forgione L, Normanno N . Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy. Explor Target Antitumor Ther. 2022; 3(2):200-223. PMC: 9400790. DOI: 10.37349/etat.2022.00079. View

12.

Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M . Genomic spectra of biliary tract cancer. Nat Genet. 2015; 47(9):1003-10. DOI: 10.1038/ng.3375. View

13.

Wang L, Zhu H, Zhao Y, Pan Q, Mao A, Zhu W . Comprehensive molecular profiling of intrahepatic cholangiocarcinoma in the Chinese population and therapeutic experience. J Transl Med. 2020; 18(1):273. PMC: 7336472. DOI: 10.1186/s12967-020-02437-2. View

14.

Nagtegaal I, Odze R, Klimstra D, Paradis V, Rugge M, Schirmacher P . The 2019 WHO classification of tumours of the digestive system. Histopathology. 2019; 76(2):182-188. PMC: 7003895. DOI: 10.1111/his.13975. View

15.

Borger D, Tanabe K, Fan K, Lopez H, Fantin V, Straley K . Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist. 2011; 17(1):72-9. PMC: 3267826. DOI: 10.1634/theoncologist.2011-0386. View

16.

Banales J, Cardinale V, Carpino G, Marzioni M, Andersen J, Invernizzi P . Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016; 13(5):261-80. DOI: 10.1038/nrgastro.2016.51. View

17.

Wang X, Zhu W, Wang Z, Huang J, Wang S, Bai F . Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities. Theranostics. 2022; 12(1):260-276. PMC: 8690927. DOI: 10.7150/thno.63417. View

18.

Goeppert B, Toth R, Singer S, Albrecht T, Lipka D, Lutsik P . Integrative Analysis Defines Distinct Prognostic Subgroups of Intrahepatic Cholangiocarcinoma. Hepatology. 2019; 69(5):2091-2106. PMC: 6594081. DOI: 10.1002/hep.30493. View

19.

Song G, Shi Y, Meng L, Ma J, Huang S, Zhang J . Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma. Nat Commun. 2022; 13(1):1642. PMC: 8960779. DOI: 10.1038/s41467-022-29164-0. View

20.

Cho S, Hwang H, Kim Y, Yoo B, Han N, Kong S . Refining Classification of Cholangiocarcinoma Subtypes via Proteogenomic Integration Reveals New Therapeutic Prospects. Gastroenterology. 2023; 164(7):1293-1309. DOI: 10.1053/j.gastro.2023.02.045. View