Circulating SCGB3A2 Is Associated With Impaired Coronary Collateralization in Patients With Chronic Total Occlusion and Type 2 Diabetes: A Proteomic Discovery and Validation Study

IF 5.9 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Pub Date : 2026-10-15 DOI:10.1111/1753-0407.70281

Jian-Jun Chen, Shuai Chen, Jia-Kang Wang, Ke Huang, An Wang, Lin Lu, Yang Dai, Feng-Hua Ding

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is associated with impaired coronary collateralization in patients with chronic total occlusion (CTO), but circulating biomarkers reflecting defective collateral remodeling remain poorly defined.

Methods

Olink proteomic profiling was performed in a discovery cohort of 88 CTO patients with T2DM stratified by collateral status. Candidate proteins were prioritized using nominal differential expression and partial least squares-discriminant analyses. Secretoglobin family 3A member 2 (SCGB3A2) was selected for validation by ELISA in an independent cohort of 832 CTO patients (425 with T2DM and 407 without diabetes). Associations with collateralization and incremental predictive value beyond clinical risk factors were evaluated.

Results

Among 265 proteins, eight showed nominal differential expression, with SCGB3A2 exhibiting the strongest signal and highest variable importance. In the T2DM cohort, serum SCGB3A2 levels were significantly higher in patients with poor collateralization and inversely correlated with Rentrop grades (both p < 0.001). SCGB3A2 remained independently associated with poor collateralization after multivariable adjustment (OR per 10 ng/mL increase, 1.63; 95% CI, 1.39–1.94; p < 0.001). Addition of SCGB3A2 to a clinical model improved discrimination with an increase in C-statistic from 0.73 to 0.78 and reclassification (NRI 0.62; IDI 0.08). Similar associations were observed in patients without diabetes.

Conclusions

Circulating SCGB3A2 is independently associated with impaired coronary collateralization in CTO patients. It may reflect biological processes underlying collateral failure and improve risk stratification, particularly in patients with T2DM.

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慢性全闭塞和2型糖尿病患者循环SCGB3A2与冠状动脉侧支受损相关：一项蛋白质组学发现和验证研究

背景：2型糖尿病（T2DM）与慢性全闭塞（CTO）患者冠状动脉侧支受损相关，但反映侧支重构缺陷的循环生物标志物仍不明确。方法：对88名CTO合并T2DM患者进行了链接蛋白质组学分析。使用标称差异表达和偏最小二乘判别分析对候选蛋白进行优先排序。分泌珠蛋白家族3A成员2 （SCGB3A2）在832例CTO患者（425例伴有T2DM， 407例无糖尿病）中通过ELISA进行验证。评估与担保和超出临床危险因素的增量预测价值的关联。结果：265个蛋白中有8个存在名义差异表达，其中SCGB3A2表达信号最强，变量重要性最高。在T2DM队列中，血清SCGB3A2水平在侧支不良患者中显著升高，且与Rentrop分级呈负相关（均为p）。结论：循环SCGB3A2与CTO患者冠状动脉侧支受损独立相关。它可能反映了侧支衰竭的生物学过程，并改善了风险分层，特别是在T2DM患者中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

2.20%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.