Faculty Collaboration Database

Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients. Clin Cancer Res 2016 Jan 01;22(1):69-78

Date

08/20/2015

Pubmed ID

26286914

Pubmed Central ID

PMC4703514

DOI

10.1158/1078-0432.CCR-15-1344

Scopus ID

2-s2.0-84954345425 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

PURPOSE: Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biologic mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves upregulation of proinflammatory genes and downregulation of genes involved in type I IFN response and antibody synthesis.

EXPERIMENTAL DESIGN: We compared pretransplant leukocyte CTRA gene expression between a group of 78 high versus low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes.

RESULTS: Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA upregulation compared with matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity, including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival.

CONCLUSIONS: Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT.

Author List

Knight JM, Rizzo JD, Logan BR, Wang T, Arevalo JM, Ma J, Cole SW

Authors

Jennifer M. Knight MD, MS Associate Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
J. Douglas Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

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

Adult
Cause of Death
Comorbidity
Female
Gene Expression Profiling
Hematopoietic Stem Cell Transplantation
Humans
Leukocytes, Mononuclear
Male
Middle Aged
Neoplasms
Patient Outcome Assessment
Prognosis
Registries
Risk Factors
Social Class
Tissue Donors
Transcriptome
Young Adult