microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis

Muhammad Nasrum Massi; Najdah Hidayah; Irda Handayani; Israini Wiyulanda Iskandar; Fathul Djannah; Nirmawati Angria; Handayani Halik

doi:10.1016/j.ncrna.2023.07.001

microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis

Noncoding RNA Res. 2023 Jul 21;8(4):527-533. doi: 10.1016/j.ncrna.2023.07.001. eCollection 2023 Dec.

Authors

Muhammad Nasrum Massi^{1

2

3}, Najdah Hidayah⁴, Irda Handayani⁵, Israini Wiyulanda Iskandar³, Fathul Djannah⁶, Nirmawati Angria⁷, Handayani Halik^{2

7}

Affiliations

¹ Department of Clinical Microbiology, Faculty of Medicine, Universitas Hasanuddin, Makassar, 90245, South Sulawesi, Indonesia.
² Hasanuddin University Medical Research Center Laboratory, Faculty of Medicine, Universitas Hasanuddin, Makassar, 90245, South Sulawesi, Indonesia.
³ Institute Research and Community Services Universitas Hasanuddin, Makassar, 90245, South Sulawesi, Indonesia.
⁴ Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), Tangerang Selatan, 15314, Banten, Indonesia.
⁵ Department of Clinical Pathology, Faculty of Medicine, Universitas Hasanuddin, Makassar, 90245, South Sulawesi, Indonesia.
⁶ Department of Anatomy Pathology, Faculty of Medicine, Universitas Mataram, Mataram, 83126, Indonesia.
⁷ Department of Biomedical Sciences, Faculty of Health Technology, Megarezky University, Makassar, 90234, South Sulawesi, Indonesia.

Abstract

Background: Studies on miRNA highlight its significance as an immunomarker for several diseases, including tuberculosis. This study aimed to determine the difference between miR-425-5p and miR-4523 expressions in patients with active pulmonary TB (PTB), latent TB infection (LTBI), and lymph node TB (LNTB), whose diagnosis remains challenging.

Methods: This case-control study was performed on blood samples obtained from 23 patients with PTB, 21 with LTBI, 21 with LNTB, and 25 healthy controls (HC). miRNA hsa-miR-425-5p and hsa-miR-4523 expression levels were measured by RT-qPCR. Statistical analyses were performed using SPSS version 25.0.

Results: RT-qPCR showed that hsa-mir-425-5p and hsa-mir-4523 expression levels were significantly different among the four groups (PTB, LTBI, LNTB, and HCs). The hsa-mir-425-5p miRNA expression level in LNTB was higher than that in LTBI (p = 0.003). Meanwhile, the hsa-mir-4523 miRNA expression was downregulated in PTB and LNTB than in LTBI (p < 0.0001 and p = 0.015, respectively). The ROC analysis of a single sample showed that only mir-4523 could discriminate LTBI and HCs, with an AUC of 0.829 (p < 0.001). The ROC curve of each miRNA was further analyzed after logistic regression by adjusting for sex and age. The combination of both miRNAs was also analyzed. The model that analyzed the combination of both miRNAs after adjusting for age had the best performance in differentiating LNTB from LTBI, with an AUC of 0.97 (p < 0.001).

Conclusion: miRNA hsa-mir-425-5p was upregulated and miRNA hsa-mir-4523 was downregulated in PTB and LNTB than in LTBI.

Keywords: Latent tuberculosis infection; Lymph node tuberculosis; Pulmonary tuberculosis; miR-425-5p; miR-4523.