Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support

• Published in: PloS one Vol. 12; no. 12; p. e0189420
• Main Authors: Bondar, Galyna, Togashi, Ryan, Cadeiras, Martin, Schaenman, Joanna, Cheng, Richard K, Masukawa, Lindsay, Hai, Josephine, Bao, Tra-Mi, Chu, Desai, Chang, Eleanor, Bakir, Maral, Kupiec-Weglinski, Sophie, Groysberg, Victoria, Grogan, Tristan, Meltzer, Joseph, Kwon, Murray, Rossetti, Maura, Elashoff, David, Reed, Elaine, Ping, Pei Pei, Deng, Mario C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.12.2017; Public Library of Science (PLoS)
• Subjects: Aberration; Analysis; Biology and Life Sciences; Biomarkers; Blood; Cancer; Correlation analysis; Deoxyribonucleic acid; DNA; Gene expression; Gene sequencing; Genes; Genetic research; Health care facilities; Heart; Heart diseases; Heart failure; Hospice care; Immunology; Implantation; Leukocytes; Liver; Liver diseases; Lymphoma; Management; Medical centers; Medical prognosis; Medical research; Medical schools; Medicine; Medicine and Health Sciences; Patient outcomes; Patients; Peripheral blood mononuclear cells; Predictions; Prognosis; Recovery (Medical); Ribonucleic acid; RNA; Services; Surgery; Survival; Transplants & implants; Los Angeles California; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189420

Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers. We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership. Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88% in Group I and 27% in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93% prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes. In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts.