Faculty Collaboration Database

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis. Blood Adv 2023 Nov 28;7(22):6830-6838

Date

09/29/2023

Pubmed ID

37773924

Pubmed Central ID

PMC10679811

DOI

10.1182/bloodadvances.2023010746

Scopus ID

2-s2.0-85178332888 (requires institutional sign-in at Scopus site)

Abstract

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Author List

Taylor MR, Cole SW, Strom J, Brazauskas R, Baker KS, Phelan R, Buchbinder D, Hamilton B, Schoemans H, Shaw BE, Sharma A, Bhatt NS, Badawy SM, Winestone LE, Preussler JM, Mayo S, Jamani K, Nishihori T, Lee MA, Knight JM

Authors

Ruta Brazauskas PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Jennifer M. Knight MD, MS Associate Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin
Rachel A. Phelan MD, MPH Associate Professor in the Pediatrics department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cross-Sectional Studies
Female
Gene Expression Profiling
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Surveys and Questionnaires
Transcriptome