Correlation of local and serum LncRNA HOTAIR expressions with disease severity of non-traumatic ONFH
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摘要:
目的探讨非创伤性股骨头坏死（ONFH）患者血清和股骨头局部LncRNA HOX转录反义RNA（HOTAIR）的表达与疾病严重程度的关系。 方法纳入本院接收的保髋或全髋置换的非创伤性ONFH患者90例，健康对照84例。RT-PCR检测血清和局部HOTAIR的表达，影像学进展由国际骨循环研究学会（ARCO）分期判定，采用VAS和Harris髋关节评分评价ONFH患者临床严重程度，应用ROC曲线确定血清HOTAIR在影像学进展中的诊断价值。 结果非创伤性ONFH患者血清HOTAIR表达高于健康对照组(1.97±0.32 vs 1.00±0.10，P < 0.001)，ONFH组织中的局部HOTAIR在坏死区高于非坏死区(2.37±0.25 vs 1.00±0.10，P < 0.001)。ARCO 4级的ONFH患者血清和局部HOTAIR表达高于3级（2.22±0.28 vs 1.94±0.36，P=0.001；2.58±0.22 vs 2.42±0.32，P=0.02）。ARCO 3级的ONFH患者与ARCO 1/2级相比，血清HOTAIR表达升高（1.94±0.36 vs 1.73±0.23，P=0.009；2.42±0.32 vs 2.13±0.24，P < 0.001）。血清中和局部HOTAIR的表达与ARCO分级呈显著正相关（r=0.569，P < 0.001；r=0.585，P < 0.001）。血清和局部HOTAIR表达与VAS评分呈正相关（血清r=0.557，P < 0.001；局部r=0.672，P < 0.001），与HSS评分呈显著负相关（血清r=-0.326，P=0.002；局部r=-0.489，P < 0.001）。ROC曲线分析显示，血清HOTAIR可作为诊断非创伤性ONFH影像学进展的良好指标(AUC=0.663, P=0.030; AUC=0.726, P=0.003)。 结论非创伤性ONFH患者血清和局部HOTAIR表达升高可能反映ONFH病情的严重程度。 -
关键词:
- LncRNA HOTAIR /
- 非创伤性股骨头坏死 /
- 疾病严重程度
Abstract:ObjectiveTo investigate the relationship between the serum and local expressions of LncRNA HOTAIR and the disease severity in patients with non- traumatic ONFH. MethodsNinety non- traumatic ONFH patients and 84 healthy controls were enrolled. RT-PCR was used to detect the expression of serum and local HOTAIR. The radiographic progression was determined by ARCO stage. The clinical severity of ONFH was evaluated by VAS and Harris hip score. ROC curve was used to determine the diagnostic value of serum HOTAIR with regard to radiographic progression. Resultsthe expression of serum HOTAIR in patients with non-traunatic ONFH was significantly higher than that in healthy controls (1.97±0.32 vs 1.00± 0.10, P < 0.001), and the local HOTAIR expression in the necrotic area was significantly higher compared with the non-necrotic area (2.37±0.25 vs 1.00±0.10, P < 0.001). The expressions of serum and local HOTAIR in ARCO 4 were significantly higher than ARCO 3(2.22±0.28 vs 1.94±0.36, P=0.001;2.58±0.22 vs 2.42±0.32, P=0.020), and the expression of serum and local HOTAIR in ARCO 3 was significantly higher than ARCO 1/2(1.94±0.36 vs 1.73±0.23, P=0.009;2.42±0.32 vs 2.13±0.24, P < 0.001). Expressions of HOTAIR in serum and local area were positively associated with ARCO grade(r=0.569, P < 0.001; r=0.585, P < 0.001), VAS score (r=0.557, P < 0.001; r=0.672, P < 0.001)and negatively related to Harris hip score(r=-0.326, P=0.002; r=-0.489, P < 0.001). Further ROC curve analysis showed that serum HOTAIR could be used as a decent indicator for the radiograohic progression of nontraumatic ONFH (AUC=0.663, P=0.030; AUC=0.726, P=0.003). ConclusionThe increase of serum and local HOTAIR expression in patients with non-traumatic ONFH may reflect the severity of the disease. -
Key words:
- LncRNA HOTAIR /
- non-traumatic necrosis of femoral head /
- disease severity
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图 2 HOTAIR在ONFH患者中的表达水平
A：激素型ONFH和酒精型ONFH血清HOTAIR相对表达水平；B：ONFH患者与对照组中血清HOTAIR相对表达水平；C：ONFH和对照组HOTAIR相对表达水平；**P<0.01.
Figure 2. HOTAIR expressions in ONFH patients.
图 3 血清与局部HOTAIR在不同ARCO分期时期的表达程度
A：血清HOTAIR在不同ARCO分期中的表达水平；B：局部HOTAIR在不同ARCO分期中的表达水平；C：血清HOTAIR与ARCO分期的相关性；D：局部HOTAIR与ARCO分期的相关性
Figure 3. Serum and local HOTAIR expressions among different ACRO stages.
图 4 ONFH患者血清与局部HOTAIR表达与临床症状严重的相关性
A：血清HOTAIR表达与VAS评分的相关性；B：局部HOTAIR表达与VAS评分的相关性；C：血清HOTAIR表达与HHS评分的相关性；D：局部HOTAIR表达与VAS评分的相关性.
Figure 4. Correlation of serum and local HOTAIR expressions with clinical severity in ONFH patients.
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[1] Choi HR, Steinberg ME, Y Cheng E. Osteonecrosis of the femoral head: diagnosis and classification systems[J]. Curr Rev Musculoskelet Med, 2015, 8(3): 210-20. doi: 10.1007/s12178-015-9278-7 [2] Okazaki S, Nagoya S, Matsumoto H, et al. Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats[J]. Lab Invest, 2015, 95(1): 92-9. doi: 10.1038/labinvest.2014.134 [3] Assouline-Dayan Y, Chang C, Greenspan A, et al. Pathogenesis and natural history of osteonecrosis[J]. Semin Arthritis Rheum, 2002, 32 (2): . http://www.ncbi.nlm.nih.gov/pubmed/12430099 [4] Mattick JS, Makunin IV. Non-coding RNA[J]. Hum Mol Genet, 2006, 15(Spec No 1): R17-R29. [5] Hong Q, Li O, Zheng W, et al. LncRNA HOTAIR regulates HIF-1α/ AXL signaling through inhibition of miR-217 in renal cell carcinoma[J]. Cell Death Dis, 2017, 8(5): e2772. http://europepmc.org/abstract/MED/28492542 [6] Wang S, Zhang X, Guo Y, et al. The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression [J]. Oncotarget, 2017, 8(15): 24449-56. doi: 10.18632/oncotarget.15511 [7] Wu KJ, Liu FL, Wu WR, et al. Long non-coding RNA HOX transcript antisense RNA (HOTAIR) suppresses the angiogenesis of human placentation by inhibiting vascular endothelial growth factor A expression[J]. Reprod Fertil Dev, 2019, 31(2): 377-85. doi: 10.1071/RD18118 [8] Jingushi S, Ohfuji S, Sofue M, et al. Osteoarthritis hip joints in Japan: involvement of acetabular dysplasia[J]. J Orthop Sci, 2011, 16(2): 156-64. doi: 10.1007/s00776-011-0025-7 [9] Yoon BH, Jones LC, Chen CH, et al. Etiologic classification criteria of ARCO on femoral head osteonecrosis part 1: glucocorticoid-associated osteonecrosis[J]. J Arthroplasty, 2019, 34 (1): 163-8. e1. doi: 10.1016/j.arth.2018.09.005 [10] Thong ISK, Jensen MP, Miró J, et al. The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure?[J]. Scand J Pain, 2018, 18(1): 99-107. doi: 10.1515/sjpain-2018-0012 [11] Shah SN, Kapoor CS, Jhaveri MR, et al. Analysis of outcome of avascular necrosis of femoral head treated by core decompression and bone grafting[J]. J Clin Orthop Trauma, 2015, 6(3): 160-6. doi: 10.1016/j.jcot.2015.03.008 [12] Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment[J]. J Am Acad Orthop Surg, 2014, 22(7): 455-64. doi: 10.5435/JAAOS-22-07-455 [13] Magnussen RA, Guilak F, Vail TP. Articular cartilage degeneration in post-collapse osteonecrosis of the femoral head. Radiographic staging, macroscopic grading, and histologic changes[J]. J Bone Joint Surg Am, 2005, 87(6): 1272-7. http://europepmc.org/abstract/MED/15930536 [14] Qi XY, Zeng YR. Biomarkers and pharmaceutical strategies in steroid-induced osteonecrosis of the femoral head: a literature review[J]. J Int Med Res, 2015, 43(1): 3-8. doi: 10.1177/0300060514554724 [15] Fernandes J, Acuña S, Aoki J, et al. Long non-coding RNAs in the regulation of gene expression: physiology and disease[J]. NcRNA, 2019, 5(1): 17. http://www.mdpi.com/2311-553X/5/1/17 [16] Wang QY, Yang QW, Chen GY, et al. LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation[J]. Sci Rep, 2018, 8(1): 9127. http://www.ncbi.nlm.nih.gov/pubmed/?term=LncRNA%20expression%20profiling%20of%20BMSCs%20in%20osteonecrosis%20of%20the%20femoral%20head%20associated%20with%20increased%20adipogenic%20and%20decreased%20osteogenic%20differentiation. [17] Wei BF, Wei W, Zhao BX, et al. Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head[J]. PLoS One, 2017, 12(2): e0169097. http://www.ncbi.nlm.nih.gov/pubmed/28207735 [18] Shehata AMF, Kamal Eldin SM, Osman NF, et al. Deregulated expression of long non-coding RNA HOX transcript antisense RNA (HOTAIR) in Egyptian patients with multiple myeloma[J]. Indian J Hematol Blood Transfus, 2020, 36(2): 271-6. doi: 10.1007/s12288-019-01211-9 [19] Jiang BM, Tang YT, Wang H, et al. Down-regulation of long non-coding RNA HOTAIR promotes angiogenesis via regulating miR-126/SCEL pathways in burn wound healing[J]. Cell Death Dis, 2020, 11(1): 61. doi: 10.1038/s41419-020-2247-0 [20] Yuan S, Zhang CX, Zhu YL, et al. Neohesperidin ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting the histone modification of lncRNA HOTAIR[J]. Drug Des Devel Ther, 2020, 14: 5419-30. http://www.ncbi.nlm.nih.gov/pubmed/33324039 -
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