Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression

Authors: HUA, XIUMENG - CHINESE ACADEMY OF MEDICAL SCIENCES; WANG, YIN-YING - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER; JIA, PEILIN - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER; XIONG, QING - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER; HU, YIQING - CHINESE ACADEMY OF MEDICAL SCIENCES; CHANG, YUAN - CHINESE ACADEMY OF MEDICAL SCIENCES; LAI, SONGQING - CHINESE ACADEMY OF MEDICAL SCIENCES; XU, YONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); ZHAO, ZHONGMING - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER; SONG, JIANGPING - CHINESE ACADEMY OF MEDICAL SCIENCES

Submitted to: BMC Complementary and Alternative Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/19/2019
Publication Date: 1/6/2020
Citation: Hua, X., Wang, Y., Jia, P., Xiong, Q., Hu, Y., Chang, Y., Lai, S., Xu, Y., Zhao, Z., Song, J. 2020. Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression. BMC Complementary and Alternative Medicine. 18(1):2 https://doi.org/10.1186/s12916-019-1469-4
DOI: https://doi.org/10.1186/s12916-019-1469-4

Interpretive Summary: Heart failure (HF) is a global pandemic with a high rate of hospitalization, morbidity, and mortality. The molecular mechanisms remain unclear. The aim of the study was to reveal potential biomarkers associated with the progression of heart failure. Here we identified COL1A1 as a biomarker for HF. These findings will guide future investigations to reveal the potential role of COL1A1 in HF development.

Technical Abstract: Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression. Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content = 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rank p value < 1.0 x 10^-4]. Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.