Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design and Study Population
2.2. Total RNA Isolation and qRT-PCR
2.3. Microarray Analysis of lncRNAs and Data Analysis
2.4. Co-Expression Network Analysis
2.5. Construction of a Competing Endogenous RNA Network
2.6. Statistical Analysis
3. Results
3.1. Basic Characteristics of the Study Subjects
3.2. lncRNA and mRNA Expression Profiles in the Plasma of SLE Patients
3.3. Selection of Candidate lncRNAs and Individual qRT-PCR Confirmation
3.4. Independent Validation of Differentially Expressed Plasma lncRNAs
3.5. Identification of lncRNAs in Plasma as Potential Biomarkers for SLE
3.6. Plasma Levels of lncRNAs in Patients with SLE, RA, and pSS
3.7. KEGG Pathway Analysis
3.8. Construction of a Co-Expression Network
3.9. Construction of a ceRNA Network
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Training Set | Testing Set |
---|---|---|
Control subjects | 80 | 40 |
Age (year) | 37 ± 14 | 34 ± 12 |
Sex (female/male) | 74/6 | 37/3 |
Patients with SLE | 160 | 80 |
Age (year) | 38 ± 14 | 38 ± 12 |
Sex (female/male) | 148/12 | 74/6 |
Disease duration (year) | 4 (1, 9) | 3 (0, 9) |
SLEDAI-2K | 12 (8, 19) | 13 ± 8 |
Disease manifestations | ||
Renal disease (%) | 63 (39) | 32 (40) |
Vasculitis (%) | 6 (4) | 4 (5) |
Arthritis (%) | 64 (40) | 26 (33) |
Myositis (%) | 12 (8) | 4 (5) |
Rash (%) | 77 (48) | 35 (44) |
Alopecia (%) | 67 (42) | 26 (33) |
Oral ulcer (%) | 30 (19) | 11 (14) |
Pleuritis (%) | 18 (11) | 8 (10) |
Leukopenia (%) | 25 (16) | 21 (26) * |
Thrombocytopenia (%) | 43 (27) | 19 (24) |
Fever (%) | 45 (28) | 20 (25) |
Nervous system disorder (%) | 41 (26) | 18 (23) |
Low complement (%) | 108 (68) | 52 (65) |
Autoantibodies | ||
Anti-dsDNA (%) | 71 (44) | 27 (34) |
Anti-Sm (%) | 53 (34) | 26 (33) |
Anti-SSA (%) | 112 (71) | 55 (71) |
Anti-SSB (%) | 26 (17) | 14 (18) |
Anti-RNP (%) | 64 (41) | 33 (42) |
Anti-Ribosomal P (%) | 48 (31) | 24 (31) |
Medical therapy | ||
Prednisone dose ≥15 mg/day (%) | 82 (51) | 42 (52) |
Prednisone dose <15 mg/day (%) | 78 (49) | 38 (48) |
Antimalarials (%) | 127 (79) | 57 (71) |
Azathioprine, MTX, or CTX (%) | 31 (19) | 11 (14) |
Characteristics | RA | pSS |
---|---|---|
Age (year) | 53.47 ± 1.63 | 47.39 ± 9.96 |
Sex (female/male) | 20/10 | 31/0 |
Disease duration (year) | 7 (3, 19) | 5.74 ± 4.40 |
Medical therapy | ||
Prednisone (%) | 20 (67) | 27 (87) |
Antimalarials (%) | 9 (30) | 24 (77) |
TGP (%) | 12 (40) | 22 (71) |
Leflunomide, MTX, or NSAID (%) | 28 (93) | 8 (26) |
lncRNAs | Healthy Controls (n = 12) | SLE Patients (n = 24) | Z | P |
---|---|---|---|---|
lnc0640 | 1.00 (0.68, 1.27) | 4.52 (3.46, 5.29) | −4.832 | <0.001 |
lnc3643 | 0.97 (0.79, 1.23) | 2.69 (1.95, 5.53) | −4.799 | <0.001 |
lnc5150 | 0.74 (0.59, 1.64) | 3.01 (1.53, 3.94) | −3.893 | <0.001 |
lnc6655 | 1.05 (0.74, 1.27) | 8.35 (5.67, 10.2) | −4.832 | <0.001 |
lnc7074 | 1.00 (0.69, 1.32) | 0.24 (0.16, 0.29) | −4.832 | <0.001 |
lnc7514 | 0.71 (0.56, 0.89) | 1.69 (1.46, 2.12) | −3.356 | <0.001 |
lncagf.1 | 0.74 (0.44, 1.68) | 2.01 (1.21, 2.95) | −3.020 | 0.002 |
lnc4688 | 1.05 (0.63, 1.16) | 0.93 (0.62, 1.27) | −0.201 | 0.856 |
lnc9603 | 0.92 (0.68, 1.34) | 0.90 (0.62, 1.06) | −0.470 | 0.655 |
lncRNA | AUC | Sensitivity | Specificity | Cutoff Point |
---|---|---|---|---|
lnc-DC | 0.683 (0.612–0.753) | 0.526 | 0.807 | 1.070 |
lnc0640 | 0.644 (0.571–0.717) | 0.421 | 0.821 | 2.250 |
lnc3643 | 0.671 (0.600–0.742) | 0.526 | 0.759 | 1.172 |
lnc5150 | 0.601 (0.527–0.675) | 0.421 | 0.772 | 2.193 |
lnc6655 | 0.631 (0.559–0.703) | 0.758 | 0.448 | 0.607 |
lnc7074 | 0.665 (0.594–0.735) | 0.632 | 0.669 | 0.673 |
lnc7514 | 0.684 (0.614–0.755) | 0.674 | 0.662 | 0.990 |
three-lncRNA panel | 0.725 (0.659–0.791) | 0.642 | 0.766 | 0.000 |
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Wu, G.-C.; Hu, Y.; Guan, S.-Y.; Ye, D.-Q.; Pan, H.-F. Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus. Biomolecules 2019, 9, 206. https://doi.org/10.3390/biom9060206
Wu G-C, Hu Y, Guan S-Y, Ye D-Q, Pan H-F. Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus. Biomolecules. 2019; 9(6):206. https://doi.org/10.3390/biom9060206
Chicago/Turabian StyleWu, Guo-Cui, Yan Hu, Shi-Yang Guan, Dong-Qing Ye, and Hai-Feng Pan. 2019. "Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus" Biomolecules 9, no. 6: 206. https://doi.org/10.3390/biom9060206