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RNA Sequencing of Whole Blood in Premature Coronary Artery Disease: Identification of Novel Biomarkers and Involvement of T Cell Imbalance

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Abstract

Serum biomarkers were explored based on the peripheral blood gene expression profiles of premature coronary artery disease (PCAD). RNA sequencing (RNA-Seq) was used to detect PCAD-specific differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (RT-PCR) was used to validate the most significant DEGs, and enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the effect on corresponding serum proteins. Fifty-nine PCAD-specific DEGs were identified. Functional analysis showed positive regulation of T cell-mediated cytotoxicity, regulation of T cell-mediated immunity, and the regulation of alpha-beta T cell proliferation which were enriched in PCAD. RT-PCR validated the significant difference in the expression of BAG6, MUC5B, and APOA2 between PCAD and late-onset coronary artery disease (LCAD) patients. ELISA validation showed serum MUC5B increased dramatically in PCAD when compared to LCAD. Our study found T cells contribute to the occurrence of PCAD, and the inflammatory factor MUC5B may be a novel serum marker in PCAD patients.

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Data Availability

Data supporting the findings of this study, including the RNA sequencing raw data, are available from the corresponding author (Y.L) upon request.

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Acknowledgements

We appreciate the work of our clinical colleagues who performed clinical data collection and all individuals who participated in this study. We thank Novogene sequencing facility for their service.

Funding

This research was supported by grants from the National Key Research and Development Program of China (2018YFE0207300), the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-124), the National Key Research and Development Program (2022YFC2009600) (2022YFC2009602), and the “Beijing Major Epidemic Prevention and Control Key Specialty Construction Project” (2022).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China

    Si Chen, Zhan Li, Haolong Li & Yongzhe Li

  2. State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

    Si Chen, Zhan Li, Haolong Li & Yongzhe Li

  3. Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Si Chen, Xiaoli Zeng & Hui Yuan

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Contributions

SC, XZ, HY and YL conceived and designed the research. ZL and HL extracted data and conducted quality assessment. SC analyzed the data and wrote the paper. All authors are accountable for all aspects of the study and attest to the accuracy and integrity of the results. All authors contributed to the article and approved the submitted version.

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Correspondence to Yongzhe Li.

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The Beijing Anzhen Hospital Ethics Committee at Capital Medical University approved this investigation (Ethics number: 2023102X). All participants signed an informed consent form.

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Chen, S., Li, Z., Li, H. et al. RNA Sequencing of Whole Blood in Premature Coronary Artery Disease: Identification of Novel Biomarkers and Involvement of T Cell Imbalance. J. of Cardiovasc. Trans. Res. (2023). https://doi.org/10.1007/s12265-023-10465-8

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