Inferences between blood microRNA, systemic inflammation and physical functioning in patients with pancreatic ductal adenocarcinoma
Britt-Marie Iresjö, Ulrika Smedh, Kent LundholmAbstract
Introduction
miRNA are small, noncoding RNA sequences for control of gene regulation in tissues, including skeletal muscles. Thus, miRNAs may be related to exercise capacity, physical performance and muscle atrophy, in progressive cancer cachexia. Therefore, we applied untargeted, large panel analyses on miRNAs in blood from patients with progressive PDAC tumours and weight loss.
Methods
2083 miRNAs were analyzed in blood plasma by HTG edge-seq miRNA whole transcriptome assay. Samples were from PDAC patients at consideration for surgery (n = 32); and at disease progression (n = 22). Controls were blood donors (n = 10). For group comparisons, global data normalization was performed to construct relative miRNA distributions, followed by Bonferroni-Dunn-corrected t-tests on log2 Foldchange values >1.5. Inferences between miRNA, systemic inflammation, physical performance, standard laboratory tests and tumor markers were evaluated by regression analyses.
Results
miR23a-5p, miR-766-5p and miR-6741-5p were significantly increased in blood samples from PDAC patients versus controls, at time for surgical considerations (P = 2.46 E-5); with strong inter-correlations among the significant miRNAs (R = 0.62–0.82, n = 64). Calculations on all PDAC patients showed that significantly increased miRNAs correlated negatively to CRP, physical performance (oxygen consumption and walking speed on treadmill; P < 0.05–0.01); and positively to s-albumin (R∼0.3, P < 0.06). miR-23a-5p and miR766-5p showed positive correlations to s-IGF-1 (P < 0.02). Karnofsky performance index was positively correlated to the significantly increased miRNAs at surgical considerations (R = 0.42–0.56; P < 0.05).
Discussion
Previous studies have linked miR-23a to exercise, and miR-766 to regulatory genes in skeletal muscles. Significant correlations among miR-23a-5p, miR-766-5p and miR-6741-5p imply impact(s) on physical functioning in PDAC patients.