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Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression
Xiumeng Hua1, Yin-Ying Wang2, Peilin Jia2
1Department of Cardiac Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 10037, China.
Insights
Collagen Type I Alpha 1 (COL1A1) shows promise as a biomarker for heart failure (HF) progression. Elevated plasma COL1A1 levels can predict poor survival within one year of heart transplantation in HF patients.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biomarker Discovery
Background:
- Heart failure (HF) is a global health crisis with significant morbidity and mortality.
- Understanding the molecular signatures of HF progression is crucial for developing effective treatments.
- Current knowledge of genetic factors influencing HF progression remains limited.
Purpose of the Study:
- To identify novel molecular biomarkers associated with heart failure progression.
- To investigate the role of specific genes in the development and advancement of HF.
- To validate potential biomarkers for predicting HF outcomes.
Main Methods:
- Generated multi-level transcriptomic data from left ventricular heart tissue of HF patients and healthy donors.
- Utilized Masson staining for fibrosis assessment and lasso regression to identify fibrosis-associated genes.
- Validated candidate genes using immunohistochemistry (IHC) and quantitative reverse transcription PCR (qRT-PCR).
- Measured plasma COL1A1 levels via ELISA in a validation cohort to predict HF progression.
Main Results:
- Differentially expressed genes (mRNAs, microRNAs, lncRNAs) were identified, potentially regulating extracellular matrix.
- COL1A1 was identified as a gene associated with fibrosis and HF progression, confirmed by IHC and qRT-PCR.
- Plasma COL1A1 levels ≥256.5 ng/ml predicted poor 1-year survival post-heart transplantation in HF patients (HR 7.4, 95% CI 3.5-15.8).
Conclusions:
- COL1A1 is a potential plasma biomarker for heart failure progression.
- Elevated COL1A1 levels are associated with adverse outcomes in HF patients awaiting transplantation.
- COL1A1 may aid in predicting short-term survival in patients with advanced heart failure.
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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