Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Srividya Vasu, Jiemin M. Yang, James Hodges, Maisam A. Abu-El-Haija, David B. Adams, Appakalai N. Balamurugan, Gregory J Beilman, Srinath Chinnakotla, Darwin L. Conwell, Martin L. Freeman, Timothy B. Gardner, Betul Hatipoglu, Varvara Kirchner, Luis F. Lara, Katherine A. Morgan, Jaimie D. Nathan, Andrew Posselt, Timothy L. Pruett, Sarah J Schwarzenberg, Vikesh K. SinghMartin Wijkstrom, Piotr Witkowski, Bashoo Naziruddin, Melena D. Bellin

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = -0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

Original languageEnglish (US)
Pages (from-to)963689721999330
JournalCell transplantation
Volume30
DOIs
StatePublished - Jan 1 2021

Keywords

  • biomarker
  • chronic pancreatitis
  • circulating miRNAs
  • islet transplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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