Expression and Clinical Significance of lncRNA NEAT1 in Patients with Spinal Tuberculosis

Spinal tuberculosis (STB) often leads to irreversible neurological injury, resulting in serious social and economic problems. With the emergence of drug resistance, the management becomes even more challenging, given the treatment courses are generally longer for skeletal than pulmonary tuberculosis (PTB). The development and validation of nonsputum biomarkers for diagnosis and tailoring of treatment duration to enable personalized and evidence-based management of such diseases to improve treatment outcomes is being called for globally. Studies have demonstrated that lncRNA NEAT1 was highly expressed in pulmonary tuberculosis (TB) and was related to its progression and recovery. However, the expression and clinical significance of lncRNA NEAT1 in STB remains unclear.

The relative expression of lncRNA NEAT1 was quantified by relative real-time reverse transcription PCR (RT-PCR). The prognostic value was assessed by receiver-operating characteristic (ROC) curve analysis. Pearson and Spearman correlation coefficient and chi-square test were used to analyze the correlation between the lncRNA NEAT1 expression and the clinical characteristics. Univariate and multivariate logistic regression analyses were used to analyze independent predictors of STB recurrence.

Compared with normal healthy individuals, the expression level of lncRNA NEAT1 in peripheral blood and granulomatous tissues of STB patients was significantly increased. The results of the in vitro Mycobacterium tuberculosis- (Mtb-) infected cell model showed that the expression level of lncRNA NEAT1 was significantly upregulated in macrophages infected with Mtb, and the difference was statistically significant compared with Mtb-uninfected group. The expression level of lncRNA NEAT1 in granulomatous tissue of STB was significantly higher than that in peripheral blood. The expression of lncRNA NEAT1 was related to segments of the lesions, paraspinal abscesses, anti-TB treatment, drug resistance, interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Multivariate analysis results showed that relatively high expression of lncRNA NEAT1_1, the shorter transcript of the NEAT1 gene, was an independent prognostic factor of STB outcome.

LncRNA NEAT1 was highly expressed in peripheral blood mononuclear cells (PBMCs) and granulomatous tissue from patients with STB, as well as in Mtb-infected THP-1 cell lines. LncRNA NEAT1 expression was significantly associated with clinical characteristics (paraspinal abscesses, segments of the lesions and anti-TB treatment, IL-6, CRP, and ESR) of patients in STB. Increased expression of lncRNA NEAT1_1 predicted good prognosis of STB and might become a prognostic biomarker for STB.