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Published in: BMC Medicine 1/2020

01-12-2020 | Heart Transplantation | Research article

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

Authors: Xiumeng Hua, Yin-Ying Wang, Peilin Jia, Qing Xiong, Yiqing Hu, Yuan Chang, Songqing Lai, Yong Xu, Zhongming Zhao, Jiangping Song

Published in: BMC Medicine | Issue 1/2020

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Abstract

Background

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.

Methods

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.

Results

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 × 10− 4].

Conclusions

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.
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Metadata
Title
Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression
Authors
Xiumeng Hua
Yin-Ying Wang
Peilin Jia
Qing Xiong
Yiqing Hu
Yuan Chang
Songqing Lai
Yong Xu
Zhongming Zhao
Jiangping Song
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1469-4

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