Protein Signatures and Tissue Diagnosis of Pancreatic Cancer

• Published in: Journal of the American College of Surgeons Vol. 230; no. 1; pp. 26 - 36.e1
• Main Authors: Underwood, Patrick W., Gerber, Michael H., Nguyen, Kathy, Delitto, Daniel, Han, Song, Thomas, Ryan M., Forsmark, Christopher E., Trevino, Jose G., Gooding, William E., Hughes, Steven J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Aged; Carcinoma, Pancreatic Ductal - chemistry; Carcinoma, Pancreatic Ductal - diagnosis; Female; Humans; Male; Middle Aged; Neoplasm Proteins - analysis; Pancreatic Neoplasms - chemistry; Pancreatic Neoplasms - diagnosis; Proteomics; Retrospective Studies; EUS; IL; IL-1RA; PDAC; ROC; FNA; AUC
• ISSN: 1072-7515; 1879-1190
• DOI: 10.1016/j.jamcollsurg.2019.10.002

Endoscopic ultrasound-guided fine-needle aspiration fails to diagnose up to 25% of patients with pancreatic ductal adenocarcinoma (PDAC). Proteomics can help to overcome this clinical dilemma. We hypothesized that soluble protein signatures can differentiate PDAC from benign tissues. Tissues were obtained from resected surgical specimens, lysed, and homogenates collected for analysis with a 41-protein multiplex assay. Analyte concentrations were normalized to total protein. Statistical analysis was performed to evaluate for differences in PDAC vs benign tissue. Tissues were obtained from 159 patients, 82 patients with PDAC naïve to therapy and 77 with benign pancreatic pathology. Fourteen analytes had a receiver operating characteristic curve area of >0.75 for predicting PDAC vs benign tissue. A recursive partitioning model using only 2 analytes, interleukin 1 receptor antagonist and transforming growth factor-α, provided an accuracy, sensitivity, and specificity of 91.2%, 90.2%, and 92.2%, respectively. A penalized logistic regression model found 12 analytes that provide diagnostic value to a protein signature. The mean area under the receiver operating characteristic after 50 tenfold cross-validations was 0.951. Accuracy, sensitivity, and specificity of this model were 91.2%, 87.8%, and 94.8%, respectively. Applying the scenario of 80% disease prevalence in patients undergoing endoscopic ultrasound with fine-needle aspiration for a pancreatic head mass, positive predictive value is 98.5% (95% CI 93.0% to 99.7%) and negative predictive value is 66.0% (95% CI 54.9% to 75.6%). Protein signatures from pancreatic specimens can differentiate PDAC from benign tissue. Additional work to validate these findings in a unique sample set is warranted. [Display omitted]