Identificação de biomarcadores de desfecho terapêutico utilizando dados públicos de transcriptomas da leishmaniose cutânea

Abstract

INTRODUCTION: Leishmaniasis is an infectious disease of global importance, characterized by ulcerative lesions with raised borders and exacerbated inflammation. The main first-line therapy, pentavalent antimony (Sb⁵⁺), has limited efficacy, with frequent treatment failure rates. In this context, transcriptomic analyses have emerged as promising tools for identifying biomarkers with predictive potential for treatment response. OBJECTIVE: This study aimed to compare transcriptional signatures from different public datasets obtained from biopsies of patients with cutaneous leishmaniasis caused by Leishmania braziliensis, followed by ex vivo validation. METHODS: Data were obtained from the repositories GSE214397 and GSE127831 (RNA-Seq, Illumina platform) and GSE55664 (microarray, Illumina platform), comparing gene expression between patients who were cured and those who experienced treatment failure with Sb⁵⁺. Subsequently, biopsies from lesions of a new clinical cohort were analyzed by RT-qPCR. Analyses included differential gene expression, correlation with clinical parameters (healing time, DTH, lesion size), ROC curve, and logistic regression. RESULTS: Exploratory analysis of GSE214397 identified ten differentially expressed genes, whose expression was correlated with treatment outcomes. Among these, two genes stood out: CCL7 and RETN, whose expression was strongly associated with therapeutic failure. These findings were validated in the new cohort by RT-qPCR. CONCLUSION: The CCL7 and RETN genes were identified as promising candidates for biomarkers of treatment failure in cutaneous leishmaniasis, with potential clinical application.