Task: Intent Identification
Input (English): One-fifth of patients with seemingly 'curable' pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed 'unresectable' by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046).", 'Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term (cancer-specific death <12 months, n\u200a=\u200a58) and long-term survivors (>30 months, n\u200a=\u200a79) who underwent resection for PDA (total, n\u200a=\u200a137). The s-TMA functions as a biological filter to identify bona fide prognostic markers associated with survival group extremes (at least 18 months separate survival groups). Based on a stringent selection process, 13 putative PDA biomarkers were identified from the public biomarker repository. Candidates were tested against the s-TMA by immunohistochemistry to identify the best markers of tumor biology. In a multivariate model, MUC1 (odds ratio, OR\u200a=\u200a28.95, 3+ vs. negative expression, p\u200a=\u200a0.004) and MSLN (OR\u200a=\u200a12.47, 3+ vs. negative expression, p\u200a=\u200a0.01) were highly predictive of early cancer-specific death. By comparison, pathologic factors (size, lymph node metastases, resection margin status, and grade) had ORs below three, and none reached statistical significance. ROC curves were used to compare the four pathologic prognostic features (ROC area\u200a=\u200a0.70) to three univariate molecular predictors (MUC1, MSLN, MUC2) of survival group (ROC area\u200a=\u200a0.80, p\u200a=\u200a0.07).
Output (English): 0