{"doi":"10.1158/1078-0432.c.6532707","title":"Data from FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with <i>FGFR2</i> Fusion Status and Immune Signatures","abstract":"<div>AbstractPurpose:<p>Selective FGFR inhibitors are effective against cholangiocarcinomas that harbor gene alterations in <i>FGFR2</i>. Clinical trials suggest that expression of wild-type FGFR mRNA can predict sensitivity to FGFR inhibitors, but this biomarker has not been well characterized in cholangiocarcinoma. This study explores the prevalence of FGFR mRNA overexpression in cholangiocarcinoma, its role in predicting sensitivity to FGFR inhibitors, and its association with immune markers.</p>Experimental Design:<p>Tissue microarrays of intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) resected between 2004 and 2015 were used to evaluate FGFR1–4 mRNA expression levels by RNA <i>in situ</i> hybridization (ISH). Expression levels of FGFR2 mRNA were correlated with <i>FGFR2</i> fusion status and with patient outcomes. Immune markers expression was assessed by IHC and CSF1 and CSF1 receptor expression were examined by RNA ISH.</p>Results:<p>Among 94 patients with resected cholangiocarcinoma, the majority had ICC (77%). <i>FGFR2</i> fusions were identified in 23% of ICCs and 5% of ECCs. High levels of FGFR mRNA in <i>FGFR2</i> fusion–negative ICC/ECC were seen for: FGFR1 (ICC/ECC: 15%/0%), FGFR2 (ICC/ECC: 57%/0%), FGFR3 (ICC/ECC: 53%/18%), and FGFR4 (ICC/ECC: 32%/0%). Overall, 62% of fusion-negative cholangiocarcinomas showed high levels of FGFR mRNA. In patients with advanced <i>FGFR2</i> fusion–positive ICC, high levels of FGFR2 mRNA did not correlate with clinical benefit. <i>FGFR2</i> fusion–positive tumors showed a paucity of PD-L1 on tumor cells.</p>Conclusions:<p>FGFR mRNA overexpression occurs frequently in cholangiocarcinoma in the absence of genetic alterations in <i>FGFR</i>. This study identifies a molecular subpopulation in cholangiocarcinoma for which further investigation of FGFR inhibitors is merited outside currently approved indications.</p></div>","journal":null,"year":2023,"id":405497,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":237346,"name":"Azfar Neyaz","orcid":"0000-0001-5321-190X","position":1,"is_corresponding":false},{"id":915691,"name":"Abhijit Chogule","orcid":"0000-0002-9358-2470","position":2,"is_corresponding":false},{"id":615857,"name":"Islam Baiev","orcid":"0000-0002-4054-2387","position":3,"is_corresponding":false},{"id":915692,"name":"Stephanie Reyes","orcid":"0000-0002-6334-6792","position":4,"is_corresponding":false},{"id":915693,"name":"Emily G. Barr Fritcher","orcid":"0000-0001-8052-563X","position":5,"is_corresponding":false},{"id":108261,"name":"Jochen K. Lennerz","orcid":"0000-0003-2434-4978","position":6,"is_corresponding":false},{"id":915694,"name":"William R. Sukov","orcid":"0000-0003-0992-2194","position":7,"is_corresponding":false},{"id":554733,"name":"Benjamin R. Kipp","orcid":"0000-0001-9477-0118","position":8,"is_corresponding":false},{"id":43401,"name":"David T. Ting","orcid":"0000-0002-3261-2322","position":9,"is_corresponding":false},{"id":13402,"name":"Vikram Deshpande","orcid":"0000-0003-4230-9308","position":10,"is_corresponding":false},{"id":258715,"name":"Lipika Goyal","orcid":"0000-0002-9777-6221","position":11,"is_corresponding":false},{"id":593672,"name":"Vishwajith Sridharan","orcid":"0000-0001-6766-2285","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:54.430249Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}