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

ABSTRACT: Background: Heart failure (HF) has been recognized as global pandemic with a high rate of associated 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 collected left ventricular heart tissue from 21 HF patients and 9 healthy donors as study cohort and generated multi-level transcriptomic data. 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 validation cohort (87 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 study cohort. The follow-up functional annotations and regulatory network reveal 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 up-regulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content >281.7 ng/ml in plasma was found to be associated with poor survival within one year of heart transplantation from heart failure [Hazard Ratio (HR): 27.52, 95% Confidence Interval (CI): 7.474 to 101.3, Log-rank p-value<1.0×10-4]. Conclusions: Our results suggested that COL1A1 is a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE135055 | GEO | 2020/01/08

REPOSITORIES: GEO