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已发表论文
环状 RNA hsa_circ_0008882 在风湿性心脏瓣膜病中的潜在诊断价值
Authors Hu Y, Li N, Sun L, Shi H, Shao G , Zhu L
Received 19 August 2025
Accepted for publication 27 October 2025
Published 14 November 2025 Volume 2025:18 Pages 6961—6973
DOI https://doi.org/10.2147/IJGM.S558257
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Redoy Ranjan
YunSong Hu,1,2,* Ni Li,1,* LeBo Sun,1 HuoShun Shi,1 GuoFeng Shao,1 LinWen Zhu1
1Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China
*These authors contributed equally to this work
Correspondence: GuoFeng Shao, Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, No. 57 Xingning Road, Yinzhou District, Ningbo, Zhejiang, 315000, People’s Republic of China, Email sgf1958@sina.com LinWen Zhu, Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, No. 57 Xingning Road, Yinzhou District, Ningbo, Zhejiang, 315000, People’s Republic of China, Email lhlzhulinwen@nbu.edu.cn
Aim: To investigate the involvement of circular RNA (circRNA) in the pathogenesis of rheumatic valvular heart disease (RVHD) and its potential use as a diagnostic biomarker.
Methods: Three differentially expressed circRNAs in RVHD were selected. Four pairs of RVHD valve tissues and non-RVHD valve tissues were verified. Plasma samples from 41 RVHD patients and 39 healthy controls were analyzed to investigate the relationship between hsa_circ_0008882 expression levels and clinical-pathological characteristics in RVHD patients, evaluating its diagnostic value for RVHD. Additional plasma samples from 47 RVHD patients and 30 controls, along with 38 valve tissues, were collected to validate the expression of downstream target genes CAMTA2 and APLN. LASSO regression combined with multivariate logistic regression analysis was employed to identify independent risk factors. The interaction between hsa_circ_0008882 and hsa-miR-4739 was validated through dual luciferase reporter assays.
Results: The expression of hsa_circ_0008882 was significantly upregulated in both plasma and valve tissue samples from RVHD patients. Plasma hsa_circ_0008882 demonstrated moderate discriminatory ability for RVHD, with an AUC of 0.707 (95% CI: 0.591– 0.823), a sensitivity of 58.5%, and a specificity of 82.1% at the optimal cutoff value. Its expression level showed significant positive correlations with multivalvular heart disease, left atrial diameter, and pulmonary artery systolic pressure. After LASSO regression screening, multivariate analysis confirmed hsa_circ_0008882 as an independent risk factor for RVHD (OR = 3.73, 95% CI: 1.75– 7.95). Mechanistic exploration revealed that hsa_circ_0008882 directly binds to hsa-miR-4739, and its potential target genes CAMTA2 and APLN were both upregulated in plasma and tissue samples from RVHD patients.
Conclusion: Hsa_circ_0008882 plays an essential role in RVHD, and its plasma expression levels may serve as a potential auxiliary diagnostic indicator for RVHD.
Keywords: circular RNA, hsa_circ_0008882, rheumatic valvular heart disease, diagnosis, noncoding RNA
1Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China
*These authors contributed equally to this work
Correspondence: GuoFeng Shao, Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, No. 57 Xingning Road, Yinzhou District, Ningbo, Zhejiang, 315000, People’s Republic of China, Email sgf1958@sina.com LinWen Zhu, Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, No. 57 Xingning Road, Yinzhou District, Ningbo, Zhejiang, 315000, People’s Republic of China, Email lhlzhulinwen@nbu.edu.cn
Aim: To investigate the involvement of circular RNA (circRNA) in the pathogenesis of rheumatic valvular heart disease (RVHD) and its potential use as a diagnostic biomarker.
Methods: Three differentially expressed circRNAs in RVHD were selected. Four pairs of RVHD valve tissues and non-RVHD valve tissues were verified. Plasma samples from 41 RVHD patients and 39 healthy controls were analyzed to investigate the relationship between hsa_circ_0008882 expression levels and clinical-pathological characteristics in RVHD patients, evaluating its diagnostic value for RVHD. Additional plasma samples from 47 RVHD patients and 30 controls, along with 38 valve tissues, were collected to validate the expression of downstream target genes CAMTA2 and APLN. LASSO regression combined with multivariate logistic regression analysis was employed to identify independent risk factors. The interaction between hsa_circ_0008882 and hsa-miR-4739 was validated through dual luciferase reporter assays.
Results: The expression of hsa_circ_0008882 was significantly upregulated in both plasma and valve tissue samples from RVHD patients. Plasma hsa_circ_0008882 demonstrated moderate discriminatory ability for RVHD, with an AUC of 0.707 (95% CI: 0.591– 0.823), a sensitivity of 58.5%, and a specificity of 82.1% at the optimal cutoff value. Its expression level showed significant positive correlations with multivalvular heart disease, left atrial diameter, and pulmonary artery systolic pressure. After LASSO regression screening, multivariate analysis confirmed hsa_circ_0008882 as an independent risk factor for RVHD (OR = 3.73, 95% CI: 1.75– 7.95). Mechanistic exploration revealed that hsa_circ_0008882 directly binds to hsa-miR-4739, and its potential target genes CAMTA2 and APLN were both upregulated in plasma and tissue samples from RVHD patients.
Conclusion: Hsa_circ_0008882 plays an essential role in RVHD, and its plasma expression levels may serve as a potential auxiliary diagnostic indicator for RVHD.
Keywords: circular RNA, hsa_circ_0008882, rheumatic valvular heart disease, diagnosis, noncoding RNA