Blood Circulating LncRNAs: SNHG5 and ZFAS1 as Biomarkers Reflecting Cachexia Incidence in Chronic Heart Failure Patients

Abstract

Background

Systemic inflammation plays a crucial role in the development and progression of chronic heart failure (CHF) across all phenotypes. The continuous release of proinflammatory cytokines causes muscle atrophy and adipocyte breakdown, ultimately resulting in cachexia. Long noncoding RNAs (lncRNAs) are emerging as potential biomarkers associated with cachexia, as they indirectly regulate muscle and fat tissue metabolism.

Objectives

This study aimed to identify inflammatory-related, plasma-circulating lncRNAs characteristic of cachexia in patients with CHF. The secondary objective was to assess the clinical utility of these selected lncRNAs as diagnostic and predictive markers for cachexia.

Methods

Blood plasma samples were collected from 157 newly diagnosed patients with CHF (91 males and 66 females; mean age: 72 ± 13 y) for lncRNA extraction. Molecular testing, using RT² lncRNA qRT-PCR Array Human Cell Development, Differentiation, and Inflammatory Panel was performed in 2 phases: the discovery phase (screening of 148 lncRNAs in 8 patients) and validation phase (validation of the identified lncRNAs in 157 patients).

Results

Five lncRNAs were found to be differentially expressed in the discovery phase. In the validation phase, 2 of these 5 lncRNAs—SNHG5 and ZFAS1—showed significant expression differences between cachectic and noncachectic patients in the entire study group (both P < 0.001). The combined downregulation of ZFAS1 and upregulation of SNHG5 was identified as an unfavorable lncRNA signature primarily associated with poor nutritional status in females (low fat-free mass, fat-free mass index, and body mass index), abnormal laboratory results (hypoalbuminemia and high concentrations of inflammatory markers), and an increased incidence of cachexia in patients with CHF. When this lncRNA signature was combined with serum C-reactive protein and albumin concentrations, it effectively differentiated between cachectic and noncachectic patients (area under the curve = 1.0). The presence of this unfavorable signature was associated with a 9-fold increased likelihood (odds ratio = 9.2) of cachexia in the study cohort.

Conclusions

The identified lncRNA signature demonstrates potential clinical value for distinguishing and predicting cachexia in patients with CHF.