Faculty Collaboration Database

Identification of Serum miRNA Signature and Establishment of a Nomogram for Risk Stratification in Patients With Pancreatic Ductal Adenocarcinoma. Ann Surg 2022 Jan 01;275(1):e229-e237

Date

05/14/2020

Pubmed ID

32398486

Pubmed Central ID

PMC7648727

DOI

10.1097/SLA.0000000000003945

Scopus ID

2-s2.0-85122290949 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. Subsequently, we used logistic regression analysis to develop models for risk stratification and Cox proportional hazard analysis to determine survival prediction probability of this signature in multiple cohorts of 433 patients with PDAC, including a tissue cohort (n = 199) and a preoperative serum cohort (n = 51).

RESULTS: We identified a panel of 9 miRNAs that were significantly upregulated (miR-205-5p and -934) or downregulated (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p) in PDAC molecular subtypes with poor survival [squamous, area under the receiver operating characteristic curve (AUC) = 0.90; basal, AUC = 0.89; and quasimesenchymal, AUC = 0.83]. The validation of this miRNA panel in a tissue clinical cohort was a significant predictor of overall survival (hazard ratio = 2.48, P < 0.0001), and this predictive accuracy improved further in a risk nomogram which included key clinicopathological factors. Finally, we were able to successfully translate this miRNA predictive signature into a liquid biopsy-based assay in preoperative serum specimens from PDAC patients (hazard ratio: 2.85, P = 0.02).

CONCLUSION: We report a novel miRNA risk-stratification signature that can be used as a noninvasive assay for the identification of high-risk patients and potential disease monitoring in patients with PDAC.

Author List

Kandimalla R, Shimura T, Mallik S, Sonohara F, Tsai S, Evans DB, Kim SC, Baba H, Kodera Y, Von Hoff D, Chen X, Goel A

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs
Middle Aged
Neoplasm Staging
Pancreatic Neoplasms
Retrospective Studies
Risk Assessment