H.S. Baig1, C. Erickson2, B. Stocker1, B. Ramser1, L. Gallagher1, C. Sublette1, S. Sen1, C. Silliman3,4,5, A. D’Alessandro2, K. Hansen2, M. Cohen1 1University of Colorado Anschutz Medical Campus, Department Of Surgery, Aurora, CO, USA 2University of Colorado Anschutz Medical Campus, Department Of Biochemistry And Molecular Genetics, Aurora, CO, USA 3University of Colorado Denver, Department Of Pediatrics And Surgery, Aurora, CO, USA 4Children’s Hospital of Colorado, Aurora, CO, USA 5Vitalant Research Institute, Vitalant Mountain Division, Denver, CO, USA
Introduction:
Despite major advances in treatment, trauma remains a leading cause of morbidity and mortality worldwide. The impact of sex dimorphisms on clinical outcomes following trauma has been reported on extensively in the trauma literature. Previous research has hypothesized that females have a survival advantage through estrogen-mediated pathways, however the molecular mechanisms underlying sex differences remain unclear. Proteomics and metabolomics have emerged as methodologies for elucidating and comparing the global landscape of biological pathways implicated in various disease states across organisms. We hypothesized that female trauma patients would exhibit significantly distinct omic signatures from male patients.
Methods:
Patients meeting the highest level of trauma activation criteria at a Level 1 Trauma Center were prospectively enrolled in this observational study. Plasma samples were collected either in the field or upon arrival to the emergency department prior to the transfusion of blood products. Male and female patients were compared to each other. Severe trauma was defined as admission base deficit ≥ 6 mmol/L and ISS ≥ 15. Proteomic and metabolomic analyses were performed using liquid chromatography-mass spectrometry. MetaboAnalyst was used for statistical analyses of omics data using univariate non-parametric comparisons. Analysis of clinical data was done with non-parametric Fisher Exact Test and Wilcoxon Rank Sum Test as appropriate. P-value ≤ 0.05 defined significance.
Results:
Two hundred ninety-two patients with omics data were included in this study. Fifty-six (20%) were female. Seventy-eight (27%) had severe trauma, of which twenty-three (30%) were female. Demographic and injury characteristics including ISS, mechanism, arrival vital signs, and base deficit were not different between groups. However, proteomic analysis shows that female patients had significantly decreased activity of complement activation, cellular metabolism, membrane transport, hemostasis, and extra-cellular matrix modification while they exhibited an up-regulation of biological pathways related to sex and reproduction, specifically SHBG (sex hormone-binding globulin).
Conclusion:
Despite similar clinical characteristics to males, female trauma patients have unique proteomic signatures distinct from their male counterparts. Future work will further investigate how sex augments the response to trauma at the cellular level. An understanding of the sex-induced differences in molecular mechanisms underlying trauma will aid the development of more personalized treatment strategies.