Expression And Clinical Significance Of Lnc RNA SOX2-OT In Peripheral Blood Mononuclear Cells Of Patients With Lupus Nephritis

Objective: The aim of this study was to determine the abnormal expression levels of long non-coding RNA SOX2 overlapping transcript(lncRNA SOX2-OT)in the peripheral blood mononuclear cells(PBMCs)of lupus nephritis(LN)patients and normal controls,as well as to assess the associations of SOX2-OT with systemic lupus erythematosus Disease Activity Index-2000(SLEDAI-2K),clinical and laboratorial features.To explore the potential role of SOX2-OT in the diagnosis and treatment of lupus nephritis,and to provide researching foundation for the early diagnosis and condition evaluation of lupus nephritis.Methods:(1)89 patients with LN who presented at the Affiliated Hospital of Youjiang Medical University for Nationalities between April 2018 and September 2019 were recruited into this study.In addition,we recruited 89 healthy controls subjects from the Health Examination Center of the Affiliated Hospital of Youjiang Medical University for Nationalities.Samples of whole blood(5 mL)were collected in evacuated tubes containing ethylene diamine tetra-acetic acid(EDTA)as the anticoagulant from each participant in both LN and healthy controls for isolating peripheral blood mononuclear cells(PBMCs).The expression of SOX2-OT in PBMCs of patients with lupus nephritis and normal controls was detected by RT-q PCR.(2)At the same time,we collected the sex,age,height,weight,urine routine,24-hour urine protein quantity,blood biochemical indexes and past medical history of lupus nephritis patients.The blood biochemical indexes include leukocyte value,platelet value,erythrocyte sedimentation rate,creatinine,complement C3,complement C4,immunoglobulin,antinuclear antibodies etc.We also recorded the sex,age,height,weight,leukocyte value and platelet value of normal controls.(3)SPSS 23.0 software was used for statistical analysis.The Kolmogorov-Smirnov test was used to test the normality of variables.Quantitative results were described by mean ± standard deviation(SD).The Student's t test was applied to the comparisons of two independent groups.ANOVA test was performed for the comparisons between groups.Nonparametric distribution data were evaluated as median values and interquartile ranges(IQR)and the Mann-Whitney U test was applied to compare the data unpaired samples.The Spearman correlation analysis was applied to analyze the correlation between lncRNA SOX2-OT and SLEDAI-2K as well as C3 and C4 levels in LN patients.The diagnostic accuracy of LN patients was performed by receiver operating characteristic(ROC)analysis,and the area under the ROC curve(AUC)was applied to estimate the diagnostic value of predicting LN compared with normal controls.All tests were two-tailed,P<0.05 were considered statistically significant.Results: The expression levels of SOX2-OT were significantly decreased in LN patients,and untreated LN patients had lower levels than treated LN patients when compared to age and sex-matched normal controls(P<0.01).SOX2-OT expression levels were significantly lower in active LN patients compared with those in inactive LN patients(P < 0.001).No apparent difference was detected between LN without and with renal damage LN patients as well as between mild and severe LN patients,respectively.The SOX2-OT expression levels in PBMCs of patients with LN were negatively correlated with SLEDAI-2K(r=-0.500,P<0.01),and positively correlated with complement C3(r=-0.461,P<0.001),complement C4(r =-0.400,P < 0.001),did not correlate with 24-hour proteinuria(r = 0.044,P = 0.727).Diagnostic biomarker differentiating LN patients(n=89)from healthy controls(n=89).Area under the curve(AUC)and P value for SOX2-OT are 0.747 and <0.001,respectively.Conclusion: The expression levels of SOX2-OT in PBMCs were significantly decreased in LN patients,and untreated LN patients had lower levels than treated LN patients when compared to normal controls.SOX2-OT expression levels were significantly lower in active LN patients compared with those in inactive LN patients,indicates that SOX2-OT might be apotential and novel biomarker in the diagnosis and therapy in LN patients.The SOX2-OT expression levels in PBMCs of patients with LN were positively correlated with complement C3 and complement C4,and negatively correlated with SLEDAI score,indicating that it may have value for evaluating LN activity.