BACKGROUND: Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS: We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS: After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS: These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.
BACKGROUND: Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS: We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS: After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS: These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.
Authors: Jennifer Permuth-Wey; Dung-Tsa Chen; William J Fulp; Sean J Yoder; Yonghong Zhang; Christina Georgeades; Kazim Husain; Barbara Ann Centeno; Anthony M Magliocco; Domenico Coppola; Mokenge Malafa Journal: Cancer Prev Res (Phila) Date: 2015-09
Authors: Jeanine Ward; Chitra Kanchagar; Isana Veksler-Lublinsky; Rosalind C Lee; Mitchell R McGill; Hartmut Jaeschke; Steven C Curry; Victor R Ambros Journal: Proc Natl Acad Sci U S A Date: 2014-08-04 Impact factor: 11.205