The role of long non-coding RNA HCP5 in ulcerative cutaneous tuberculosis therapy introduction

Ulcerative Cutaneous Tuberculosis (UCT) represents a diagnostically complex variant of extrapulmonary tuberculosis, characterized by the absence of standardized biomarkers for monitoring treatment efficacy.

This study sought to explore the potential of lncRNA HCP5 as a diagnostic and therapeutic biomarker for UCT.

We conducted an integrated bioinformatics analysis on clinical samples from patients with UCT and Non-Tuberculous Cutaneous Ulcers to identify differentially expressed lncRNAs. Co-expression networks were developed to associate HCP5 with downstream mRNAs. Validation was performed using patient tissue samples and an in vitro model of BCG-infected macrophages, incorporating functional knockdown studies. Longitudinal profiling of UCT patients undergoing therapy was employed to evaluate the dynamics of the biomarker.

Our investigation identified 1,994 differentially expressed long non-coding RNAs (lncRNAs), with HCP5 being notably upregulated. Through co-expression analysis, HCP5 was linked to immune and inflammation pathways, and 12 correlated mRNAs were identified, among which ITGB2 was validated as a downstream target. The knockdown of HCP5 resulted in a significant reduction of ITGB2 expression in macrophages. Longitudinal analysis demonstrated a significant decline in both HCP5 and ITGB2 levels in patient tissues and plasma following two weeks of anti-tuberculosis treatment.

This study elucidates a novel HCP5/ITGB2 regulatory axis in the pathogenesis of UCT and highlights their dynamic responsiveness to therapeutic intervention. These findings address a critical clinical gap by providing objective biomarkers for the diagnosis and monitoring of treatment efficacy in cutaneous tuberculosis.