Protein biomarker of cell proliferation determines survival to discharge in cases of equine large colon volvulus

Abstract

Progenitor cells play critical roles in epithelial repair following ischaemic injury. Protein biomarkers have been used to identify intestinal progenitor cell subpopulations. This study aims to determine if a critical number of intestinal progenitor cells can predict tissue viability and survival to discharge of large colon volvulus (LCV) cases. The objectives were to 1) identify intestinal progenitor cell subpopulations using biomarkers: proliferating cell nuclear antigen (PCNA), sex determining region Y box 9 (SOX9), phospho-histone H3 (PHH3) and Ki-67, 2) define cut-off values for critical numbers of positive cells and 3) determine if survival to discharge is associated with cut-off values. Retrospective cohort study. Adult horses admitted to the Farm and Equine Veterinary Medical Center at NC State's Veterinary Hospital and Peterson and Smith Equine Hospital between 2006 and 2016 that underwent an exploratory coeliotomy with a diagnosis of LCV of ≥360 degrees, had pelvic flexure biopsy and that recovered from general anaesthesia were selected for inclusion in the study. Immunohistochemical analyses were performed and positive cells were counted. Optimal cut-off values were determined using receiver operator curves. A Fisher's exact test was used to associate cut-off values with survival to discharge. In this study, 23 cases of LCV ≥360° were included. Of 23 horses, 13 (57%) survived to discharge. A cut-off value of <2.1 PHH3 positive cells per crypt correctly predicted death with 100% sensitivity (95% CI; 69.15-100%) and 84.62% specificity (95% CI; 54.55-98.08%). LCV cases with <2.1 PHH3 positive cells per crypt were 96.6 times more likely to die (95% CI; 4.14-2255 and P<0.0001). Biomarkers PCNA, SOX9 and Ki-67 did not predict short-term survival. The population size was small. PHH3 immunohistochemical analysis may assist in more accurate prediction of survival to hospital discharge of LCV cases. The summary is available in Spanish - see Supporting Information.