{"doi":"10.3390/cancers13205168","title":"Development of a MicroRNA Signature Predictive of Recurrence and Survival in Pancreatic Ductal Adenocarcinoma","abstract":"Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34; 95%CI 1.27–11.38; p = 0.017) and OS (HR = 2.89; 95%CI 1.10–4.76; p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39; 95%CI 1.03–5.54; p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71; 95%CI 1.14–6.48; p = 0.025), DR (HR = 1.93; 95%CI 1.10–3.38; p = 0.022), and OS (HR = 1.97; 95%CI 1.17–3.34; p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p < 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.","journal":"Cancers","year":2021,"id":205409,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8268,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":380161,"name":"Amy Webb","orcid":"0000-0001-5503-7300","position":1,"is_corresponding":false},{"id":497440,"name":"Kenneth W. Merrell","orcid":"0000-0002-3831-5644","position":2,"is_corresponding":false},{"id":227744,"name":"Eugene J. Koay","orcid":"0000-0001-7675-3461","position":3,"is_corresponding":false},{"id":380159,"name":"Adam R. Wolfe","orcid":"0000-0002-0123-7371","position":4,"is_corresponding":false},{"id":788730,"name":"Lizhi Zhang","orcid":"0000-0001-5829-9234","position":5,"is_corresponding":false},{"id":789191,"name":"T.J. Wilhite","orcid":null,"position":6,"is_corresponding":false},{"id":315003,"name":"Dalia Elganainy","orcid":"0000-0003-4427-986X","position":7,"is_corresponding":false},{"id":380163,"name":"Ryan Robb","orcid":"0000-0001-7661-7902","position":8,"is_corresponding":false},{"id":325041,"name":"Wei Chen","orcid":"0000-0003-4610-8490","position":9,"is_corresponding":false},{"id":334148,"name":"Jordan M. Cloyd","orcid":"0000-0002-2373-8433","position":10,"is_corresponding":false},{"id":334150,"name":"Mary Dillhoff","orcid":"0000-0001-6589-7072","position":11,"is_corresponding":false},{"id":242172,"name":"Allan Tsung","orcid":"0000-0002-3916-8965","position":12,"is_corresponding":false},{"id":381025,"name":"Laith Abushahin","orcid":"0000-0001-5155-1185","position":13,"is_corresponding":false},{"id":288342,"name":"Anne M. Noonan","orcid":"0000-0001-8083-8492","position":14,"is_corresponding":false},{"id":288341,"name":"Terence M. Williams","orcid":"0000-0002-1020-0845","position":15,"is_corresponding":false},{"id":380162,"name":"Nikhil Sebastian","orcid":"0000-0002-3977-7867","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:51:33.996102Z","pmid":"34680317","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":[]}