{"doi":"10.1200/jco.23.01573","title":"Using Tumor Marker Gene Variants to Improve the Diagnostic Accuracy of DUPAN-2 and Carbohydrate Antigen 19-9 for Pancreatic Cancer","abstract":"PURPOSE Circulating carbohydrate antigen 19-9 (CA19-9) levels reflect FUT3 and FUT2 fucosyltransferase activity. Measuring the related glycan, DUPAN-2, can be useful in individuals unable to synthesize CA19-9. We hypothesized that similar to CA19-9, FUT functional groups determined by variants in FUT3 and FUT2 influence DUPAN-2 levels, and having tumor marker reference ranges for each functional group would improve diagnostic performance. MATERIALS AND METHODS Using a training/validation study design, FUT2/ FUT3 genotypes were determined in 938 individuals from Johns Hopkins Hospital: 607 Cancer of the Pancreas Screening (CAPS) study subjects with unremarkable pancreata and 331 with pancreatic ductal adenocarcinoma (PDAC). Serum DUPAN-2 and CA19-9 levels were measured by immunoassay. RESULTS In controls, three functional FUT groups were identified with significant differences in DUPAN-2 levels: FUT3-intact, FUT3-null/FUT2-intact, and FUT3-null/FUT2-null. DUPAN-2 training set diagnostic cutoffs for each FUT group yielded higher diagnostic sensitivity in the validation set for patients with stage I/II PDAC than uniform cutoffs (60.4% [95% CI, 50.2 to 70.0] v 39.8% [30.0 to 49.8]), at approximately 99% (96.7 to 99.6) specificity. Combining FUT/CA19-9 and FUT/DUPAN-2 tests yielded 78.4% (72.3 to 83.7) sensitivity for stage I/II PDAC, at 97.7% (95.3 to 99.1) specificity in the combined sets, with higher AUC (stage I/II: 0.960 v 0.935 for CA19-9 + DUPAN-2 without the FUT test; P < .001); for stage I PDAC, sensitivity was 62.0% (49.1 to 73.2; AUC, 0.919 v 0.883; P = .03). CA19-9 levels in FUT3-null/FUT2-null PDAC subjects were higher than in FUT3-null/FUT2-intact subjects (median/IQR; 24.9/57.4 v <1/2.3 U/mL; P = .0044). In a simulated CAPS cohort, AUC precision recall (AUC PR ) scores were 0.51 for CA19-9 alone, 0.64 for FUT/CA19-9, 0.73 for CA19-9/DUPAN-2, and 0.84 for FUT/CA19-9/DUPAN-2. CONCLUSION Using a tumor marker gene test to individualize CA19-9 and DUPAN-2 reference ranges achieves high diagnostic performance for stage I/II pancreatic cancer.","journal":"Journal of Clinical Oncology","year":2024,"id":420597,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281030,"name":"Mohamad Dbouk","orcid":"0000-0002-6055-0202","position":1,"is_corresponding":false},{"id":283338,"name":"Takeichi Yoshida","orcid":null,"position":2,"is_corresponding":false},{"id":1041496,"name":"Helena Saba","orcid":"0009-0004-0973-9116","position":3,"is_corresponding":false},{"id":1041497,"name":"Elizabeth Abou Diwan","orcid":"0009-0007-4264-9982","position":4,"is_corresponding":false},{"id":1212087,"name":"Kanako Yoshida","orcid":"0000-0001-5745-3623","position":5,"is_corresponding":false},{"id":1041500,"name":"Ali Dbouk","orcid":"0009-0001-0566-141X","position":6,"is_corresponding":false},{"id":237759,"name":"Amanda L. Blackford","orcid":"0000-0002-6519-4833","position":7,"is_corresponding":false},{"id":742915,"name":"Ming-Tseh Lin","orcid":null,"position":8,"is_corresponding":false},{"id":109467,"name":"Anne Marie Lennon","orcid":"0000-0001-8957-3945","position":9,"is_corresponding":false},{"id":266833,"name":"Richard A. Burkhart","orcid":"0000-0003-1087-0870","position":10,"is_corresponding":false},{"id":294320,"name":"Jin He","orcid":"0000-0001-9149-2247","position":11,"is_corresponding":false},{"id":60419,"name":"Lori J. Sokoll","orcid":"0000-0001-5130-0060","position":12,"is_corresponding":false},{"id":62913,"name":"James R. Eshleman","orcid":"0000-0002-9274-8459","position":13,"is_corresponding":false},{"id":237760,"name":"Marcia Irene Canto","orcid":"0000-0002-2193-3032","position":14,"is_corresponding":false},{"id":68540,"name":"Michael Goggins","orcid":"0000-0002-4286-2296","position":15,"is_corresponding":false},{"id":1041495,"name":"Yohei Ando","orcid":"0009-0002-4005-038X","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:57:31.041511Z","pmid":"38457748","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":[]}