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A serum-induced transcriptome and serum cytokine signature obtained at diagnosis correlates with the development of early pancreatic ductal adenocarcinoma metastasis

ABSTRACT: Immune indicators of PDAC progression were obtained from peripheral blood and analyzed in the context of each other by calculating a serum-induced transcriptome index and a serum cytokine index. Significant correlation of the transcriptome index with the inflammatory transcriptome index suggest that inflammtion has a role in PDAC progression. The segregation of metastatic progressed and not progressed patients when the inflammatory transcriptome index was analyzed in the context of the serum cytokine index suggest that the serum cytokine index may be a systemic biomarker of PDAC progression . Our data illustrates both the transcriptome and cytokine indices have promise as biomarkers of cancer immunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107818 | GEO | 2018/12/31

REPOSITORIES: GEO

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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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A serum-induced transcriptome and serum cytokine signature obtained at diagnosis correlates with the development of early pancreatic ductal adenocarcinoma metastasis

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