Differential Gene Expression of ASUN, NEMF, PTPRC and DHX29: Candidate Biomarkers for the Diagnosis of Active and Latent Tuberculosis

Abstract

Introduction: Tuberculosis (TB) remains one of the most important infectious causes of death throughout the world. A wide range of technologies have been used for the diagnosis of TB. However, current diagnostic tests are inadequate. The aim of this study was to evaluate the expression of four genes, namely ASUN, NEMF, PTPRC and DHX29 as candidate biomarkers for the diagnosis of Latent tuberculosis infection (LTBI) and active TB and discrimination of active TB and LTBI. Material and Methods: The expression of the mentioned four genes as well as ACTB as a housekeeping gene was evaluated by real-time PCR. Receiver operating characteristic (ROC) curve analysis was conducted to assess the specificity and sensitivity of each validated biomarker. Results: Our results showed that the expression of theASUN gene could discriminate between active TB cases and healthy BCG vaccinated volunteers with an AUC value of 0.76, combing with a sensitivity of 68% and a specificity of 67%. It should be noted that the PTPRC gene also has the potential for the diagnosis of active TB with an AUC value of 0.67 and a sensitivity of 64.5% and a specificity of 70%. The curve revealed that cases with LTBI could be distinguished from healthy BCG vaccinated volunteers according to their expression of the ASUN gene with an AUC value of 0.81. The cut-off value for diagnosing was 11, with a sensitivity of 73% and a specificity of 79%. Moreover, the expression of the NEMF gene might be considered as a diagnostic tool for the diagnosis of LTBI. The analysis showed an AUC value of 0.75. The highest sensitivity (60%) and specificity (81%) were obtained with a cut off value of 12. Conclusion: According to our results, the expression of ASUN and NEMF genes might be considered as a diagnostic tool for the diagnosis of LTBI. Our study showed that the expression of ASUN and PTPRC was obviously higher in active TB patients than those in healthy BCG vaccinated controls. On the other hand, DHX29 and PTPRC genes might be helpful in differentiating active TB and LTBI. However, our findings deserve further validation in larger studies.