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ORIGINAL RESEARCH article
Front. Clin. Diabetes Healthc.
Sec. Diabetes, Lifestyle and Metabolic Syndrome
Volume 6 - 2025 | doi: 10.3389/fcdhc.2025.1523112
This article is part of the Research Topic Metabolic Syndrome in Patients with Diabetes: Identification of Biomarkers View all 6 articles
ST18 as a promising molecular candidate in depression linked to diabetes: Insights from untargeted proteomics
Provisionally accepted- 1 All India Institute of Medical Sciences, Rishikesh, Rishikesh, India
- 2 All India Institute of Medical Sciences, New Delhi, National Capital Territory of Delhi, India
Depression in diabetic patients is linked to a higher rate of hospitalization and healthcare costs. This bidirectional relationship complicates both mental and physical health, making it a critical area of concern in healthcare. A comorbid condition that remains largely undiagnosed due to the absence of reliable biomarkers. To address this gap, we employed untargeted proteomic profiling using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to identify differentially expressed proteins in the serum of individuals with type 2 diabetes mellitus (T2DM) and comorbid depression.In the discovery cohort, we performed a comparative analysis of protein expression among healthy controls, T2DM patients, and T2DM patients with depression. 18 samples were processed by LC/MS for proteomic analysis. The proteomic dataset was then analyzed using Metaboanalyst 6.0. proteinprotein interaction and pathway analysis for differentially expressed proteins were carried out using STRING database. A total of 242 proteins were identified, with 12 significantly dysregulated across the groups; 9 of these were specific to T2DM patients with depression. Validation of three candidate proteins was conducted using ELISA on serum samples from healthy controls (n=30), T2DM (n=30), and T2DM with depression (n=30) . Among the three validated proteins (LRG1, APOC2 and ST18), the expression of ST18 transcription factor showed a significant increase in T2DM with depression samples. Moreover, ST18 had the maximum AUC based on receiver operating characteristic curve.These findings suggest that ST18, might be associated with the development of depression in T2DM individuals. Future longitudinal studies with larger cohorts are necessary to establish a causal relationship between T2DM and depression progression.
Keywords: ST18 transcription factor, Depression, gene ontology, Type2 diabetes milletus, untargeted protein profiling, LC/MS-MS
Received: 05 Nov 2024; Accepted: 05 Feb 2025.
Copyright: © 2025 Singh, Bandyopadhyay, sen, Kant, Das and Saha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiya Singh, All India Institute of Medical Sciences, Rishikesh, Rishikesh, India
Sarama Saha, All India Institute of Medical Sciences, Rishikesh, Rishikesh, India
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