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PDAC prognosis biomarker in genomic and transcriptomic molecular data

ABSTRACT: PDAC prognosis biomarker in genomic and transcriptomic molecular data

PROVIDER: PRJNA701088 | ENA |

REPOSITORIES: ENA

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Project description:Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures predict survival of early-stage PDAC. Methods: Se-rum RNA from archival 15 stage I-III PDAC patients and 4 controls was used for miRNAs ex-pression profile (Agilent microarrays). PDAC patients with comparable age, gender, diabetes, jaundice and surgery were classified according to survival: less than 14 months (7/15 pts, group A) and more than 22 months (8/15 pts, group B). Bioinformatic data analysis was performed by two-class Significance Analysis of Microarray (SAM) algorithm. Binary logistic regression analyses considering PDAC diagnosis and outcome as dependent variables, and ROC analyses were also performed. Results: 2549 human miRNAs were screened out. At SAM, 76 differen-tially expressed miRNAs were found among controls and PDAC (FDR = 0.4%), the large major-ity (50/76, 66%) of them being downregulated in PDAC with respect to controls. Six miRNAs were independently correlated with early PDAC, and among these, hsa-miR-6821-5p was asso-ciated with the best ROC curve area in distinguishing controls from early PDAC. Among the 71 miRNAs differentially expressed between groups A and B, the most significant were hsa-miR-3135b expressed in group A only, hsa-miR-6126 and hsa-miR-486-5p expressed in group B only. Eight miRNAs were correlated with the presence of lymph-node metastases; among these, hsa-miR-4669 is of potential interest. hsa-miR-4516, increased in PDAC and found as an independent predictor of survival, has among its putative targets a series of gens involved in key pathways of cancer progression and dissemination, such as Wnt and p53 signaling pathways. Conclusions: A series of serum miRNAs was identified as potentially useful for the early diag-nosis of PDAC, and for establishing a prognosis

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PDAC prognosis biomarker in genomic and transcriptomic molecular data

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