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 pro-inflammatory cytokines causes muscle atrophy and adipocyte breakdown, ultimately resulting in cachexia. Long non-coding RNAs (lncRNAs) are emerging as potential biomarkers associated with cachexia, as they indirectly regulate muscle and fat tissue metabolism.

Purpose: This study aimed to identify inflammatory-related, plasma-circulating lncRNAs characteristic of cachexia in CHF patients. 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 CHF patients (91 men and 66 women; mean age: 72±13 years) for lncRNA extraction. Molecular testing, using RT² lncRNA qRT-PCR Array Human Cell Development, Differentiation, and Inflammatory Panel was performed in two phases: the discovery phase (screening of 148 lncRNAs in 8 patients) and the validation phase (validation of the identified lncRNAs in 157 patients).

Results: Five lncRNAs were found as differentially expressed in the discovery phase. In the validation phase, two of these five lncRNAs: SNHG5 and ZFAS1, showed significant expression differences between cachectic and non-cachectic 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 women (low fat-free mass, fat-free mass index and body mass index), abnormal laboratory results (hypoalbuminemia and high levels of inflammatory markers), and an increased incidence of cachexia in CHF patients. When this lncRNA signature was combined with serum CRP and albumin levels, it effectively differentiated between cachectic and non-cachectic patients (AUC=1.0). The presence of this unfavorable signature was associated with a 9-fold increased likelihood (OR=9.2) of cachexia in the study cohort.

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