Development of a microrna signature predictive of recurrence and survival in pancreatic ductal adenocarcinoma

Nikhil T. Sebastian, Amy Webb, Kenneth W. Merrell, Eugene J. Koay, Adam R. Wolfe, Lizhi Zhang, Tyler J. Wilhite, Dalia Elganainy, Ryan Robb, Wei Chen, Jordan Cloyd, Mary Dillhoff, Allan Tsung, Laith Abushahin, Anne Noonan, Terence M. Williams

Research output: Contribution to journalArticlepeer-review


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 insti-tutions 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 NanoS-tring, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training co-hort, 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.

Original languageEnglish (US)
Article number5168
Issue number20
StatePublished - Oct 1 2021


  • Adjuvant radia-tion
  • Local recurrence
  • Locoregional recurrence
  • MicroRNA
  • Neoadjuvant radiation
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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