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Peer-reviewedCC BYMolecular biomedicine

Cat eye syndrome chromosome region, candidate 1 is a novel prognostic biomarker in hypertrophic cardiomyopathy.

  • Yu Zhang1,2
  • Fangfang Wan2
  • Chen Li3
  • Bo Wang4
  • Mo Zhang1
  • Minjie Lu2
  • Lianming Kang1
  • Liwen Liu5
  • Jizheng Wang6
  • Lei Song7,8,9
9 affiliations
  1. 1Cardiomyopathy Ward, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  2. 2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  3. 3Center of Coronary Artery Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
  4. 4Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  5. 5Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. [email protected].
  6. 6State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
  7. 7Cardiomyopathy Ward, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
  8. 8State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
  9. 9National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
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Abstract

Hypertrophic cardiomyopathy (HCM) exhibits great prognostic heterogeneity, necessitating the identification of high-risk patients for timely treatment. This study aimed to find novel prognostic biomarkers directly from diseased cardiac tissue to improve risk stratification of HCM. We utilized a myocardial transcriptome discovery cohort (n = 246; median follow-up 6.8 years) alongside two independent plasma validation cohorts (Beijing, n = 1,238; follow-up 2.5 years; Xi'an, n = 402; follow-up 4.8 years). The primary and secondary endpoints were cardiovascular death and sudden cardiac death (SCD), respectively. In the discovery cohort, myocardial expression of CECR1 (cat eye syndrome chromosome region, candidate 1, also known as ADA2, Adenosine Deaminase 2) demonstrated the strongest association with cardiovascular death (P = 9.6 × 10⁻⁵). Plasma CECR1 levels correlated modestly but significantly with myocardial expression. In the Beijing validation cohort, decreased plasma CECR1 predicted increased risks of cardiovascular death (adjusted hazard ratio (HR) 3.731, P < 0.001) and SCD (adjusted HR 7.398, P < 0.001), with areas under the curves (AUCs) of 0.720 and 0.798, respectively. These findings were replicated in the Xi'an validation cohort. Integrating plasma CECR1 into the HCM Risk-SCD model significantly enhanced its predictive performance, increasing the AUC from 0.723 to 0.845 (P = 0.031) in the Beijing validation cohort and consistently improving it from 0.600 to 0.781 (P = 0.018) in the Xi'an validation cohort. In conclusion, CECR1 represents a novel prognostic biomarker of HCM. Measurement of CECR1 may improve risk stratification by facilitating the identification of individuals at higher risk of cardiovascular mortality. CECR1 assessment may provide additional information for SCD risk evaluation and support clinical decision-making regarding implantable cardioverter-defibrillator therapy.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026syndrome,
  title = {{Cat eye syndrome chromosome region, candidate 1 is a novel prognostic biomarker in hypertrophic cardiomyopathy.}},
  author = {Yu Zhang and Fangfang Wan and Chen Li and Bo Wang and Mo Zhang and Minjie Lu and Lianming Kang and Liwen Liu and Jizheng Wang and Lei Song},
  journal = {Molecular biomedicine},
  year = {2026},
  month = oct,
  doi = {10.1186/s43556-026-00648-5},
  url = {https://europepmc.org/article/MED/42961724},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cat eye syndrome chromosome region, candidate 1 is a novel prognostic biomarker in hypertrophic cardiomyopathy.
AU  - Yu Zhang
AU  - Fangfang Wan
AU  - Chen Li
AU  - Bo Wang
AU  - Mo Zhang
AU  - Minjie Lu
AU  - Lianming Kang
AU  - Liwen Liu
AU  - Jizheng Wang
AU  - Lei Song
PY  - 2026
DA  - 2026/10/30
JO  - Molecular biomedicine
DO  - 10.1186/s43556-026-00648-5
UR  - https://europepmc.org/article/MED/42961724
AB  - Hypertrophic cardiomyopathy (HCM) exhibits great prognostic heterogeneity, necessitating the identification of high-risk patients for timely treatment. This study aimed to find novel prognostic biomarkers directly from diseased cardiac tissue to improve risk stratification of HCM. We utilized a myocardial transcriptome discovery cohort (n = 246; median follow-up 6.8 years) alongside two independent plasma validation cohorts (Beijing, n = 1,238; follow-up 2.5 years; Xi'an, n = 402; follow-up 4.8 years). The primary and secondary endpoints were cardiovascular death and sudden cardiac death (SCD), respectively. In the discovery cohort, myocardial expression of CECR1 (cat eye syndrome chromosome region, candidate 1, also known as ADA2, Adenosine Deaminase 2) demonstrated the strongest association with cardiovascular death (P = 9.6 × 10⁻⁵). Plasma CECR1 levels correlated modestly but significantly with myocardial expression. In the Beijing validation cohort, decreased plasma CECR1 predicted increased risks of cardiovascular death (adjusted hazard ratio (HR) 3.731, P < 0.001) and SCD (adjusted HR 7.398, P < 0.001), with areas under the curves (AUCs) of 0.720 and 0.798, respectively. These findings were replicated in the Xi'an validation cohort. Integrating plasma CECR1 into the HCM Risk-SCD model significantly enhanced its predictive performance, increasing the AUC from 0.723 to 0.845 (P = 0.031) in the Beijing validation cohort and consistently improving it from 0.600 to 0.781 (P = 0.018) in the Xi'an validation cohort. In conclusion, CECR1 represents a novel prognostic biomarker of HCM. Measurement of CECR1 may improve risk stratification by facilitating the identification of individuals at higher risk of cardiovascular mortality. CECR1 assessment may provide additional information for SCD risk evaluation and support clinical decision-making regarding implantable cardioverter-defibrillator therapy.
SN  - 2662-8651
ER  -