长链非编码RNA在精神分裂症的变化与阳性、阴性症状的研究

doi:10.3877/cma.j.issn.2095-123X.2017.02.004

中华脑科疾病与康复杂志(电子版) ›› 2017, Vol. 07 ›› Issue (02) : 64 -70. doi: 10.3877/cma.j.issn.2095-123X.2017.02.004

所属专题：精准医疗；总编推荐；文献；

临床研究

长链非编码RNA在精神分裂症的变化与阳性、阴性症状的研究

何明骏¹, 姚高峰¹^,^†(

), 张理义¹, 孔令明¹, 牛威¹, 陈升东¹, 仲爱芳¹

^1. 213000　江苏常州，解放军102医院全军心理疾病防治中心

收稿日期:2016-09-05 出版日期:2017-04-01
通信作者: 姚高峰
基金资助:
中国人民解放军总后勤部科研基金"十二五"重大项目(编号：BWS14J027)

A study on the relation of positive and negative symptoms to long non-coding RNAs with altered expressions in schizophrenia

Mingjun He¹, Gaofeng Yao¹^,^†(), Liyi Zhang¹, Lingming Kong¹, Wei Niu¹, Shendong Chen¹, Aifang Zhong¹

^1. Prevention and Treatment Center for Psychological Diseases, No.102 Hospital of the Chinese People′s Liberation Army, Changzhou 213003, China

Received:2016-09-05 Published:2017-04-01
Corresponding author: Gaofeng Yao
About author:
Corresponding author: Yao Gaofeng, Email: yao_gaofeng@126.com

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引用本文：

何明骏, 姚高峰, 张理义, 孔令明, 牛威, 陈升东, 仲爱芳. 长链非编码RNA在精神分裂症的变化与阳性、阴性症状的研究[J]. 中华脑科疾病与康复杂志(电子版), 2017, 07(02): 64-70.

Mingjun He, Gaofeng Yao, Liyi Zhang, Lingming Kong, Wei Niu, Shendong Chen, Aifang Zhong. A study on the relation of positive and negative symptoms to long non-coding RNAs with altered expressions in schizophrenia[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2017, 07(02): 64-70.

目的

探讨精神分裂症外周血长链非编码RNA(lncRNA)差异表达及其与阳性、阴性症状的关系。

方法

采用基因芯片筛查病例组与正常对照组之间有差异表达的lncRNA。2012年8月至2014年6月于解放军第102医院门诊以及精神科病房连续入组的96例患者和44例健康对照者，用qPCR进行验证。并用曼-惠特尼U检验、t检验、相关分析等分析精神分裂症患者lncRNA表达量与阳性、阴性症状的相关性。

结果

1．病例组结果显示，与对照组比较，其外周血单核细胞中3种lncRNA(NONHSAT021545、NONHSAT089447、NONHSAT098126)表达显著上调，差异有统计学意义(t＝－2.460～－2.038，P<0.05)。2.精神分裂症中有差异表达的lncRNA与精神分裂症阳性、阴性症状量表分(PANSS)的相关分析提示，有差异表达的10种lncRNA均与精神分裂症阳性症状量表分显著正相关(r＝0.231～0.276, P均<0.05)。3.精神分裂症中有差异表达的lncRNA与阳性、阴性症状量表各因子分的相关分析显示，有差异表达的10种lncRNA均与激活性显著正相关(r＝0.243～0.352, P均<0.05); TCONS_l2_00025502、ENST00000563823、ENST00000521622、TCONS_l2_00021339及NONHSAT104778与偏执显著正相关(r＝0.201～0.223, P<0.05);有差异表达的10种lncRNA均与攻击性显著正相关(r＝0.207～0.259, P<0.05)。4.对高表达与低表达组的阳性、阴性症状进行比较发现，NONHSAT021545、NONHSAT041499高表达组的激活性和攻击性得分显著低于低表达组(P均<0.05)。

结论

lncRNA的异常表达可能与精神分裂症有某种关联，某些异常表达的lncRNA与特定的阳性、阴性症状特征关系密切。

关键词: 精神分裂症, 长链非编码RNA, 生物标记物, 阳性与阴性症状量表

Objective

To explore the relation of positive and negative symptoms to long non coding RNAs (lncRNAs) with altered expressions in peripheral blood of schizophrenia.

Methods

Gene microarray was used to screen the lncRNAs which expressed differently in case group compared to that in control group, and the screened lncRNAs were validated by real-time fluorescence quantitative PCR(qRT-PCR) in 96 schizophrenic patients in the outpatient service and psychiatric wards of No.102 Hospital of the Chinese People′s Liberation Army and 44 healthy people from Auguest 2012 to June 2014. And Mann-Whitney U test, t test and correlation analysis were used to analyze the correlations of positive and negative symptoms with the expression levels of lncRNAs in schizophrenic patients.

Results

1. Compared to control group, 3 lncRNAs(NONHSAT021545、NONHSAT089447、NONHSAT098126) in case group were greatly high-regulated and the differences were statistically significant (t=-2.460~-2.038, P<0.05). 2. The correlation analysis on differentially-expressed lncRNAs with the scores of positive and negative symptom scale (PANSS) revealed that PR1~PR10 with altered expressions were positively associated with the scores of positive and negative symptom scale (r=0.231~0.276, all P<0.05). 3. PR1~PR10 with altered expressions were positively correlated to activation(r=0.243~0.352, all P<0.05); TCONS_l2_00025502、ENST00000563823、ENST00000521622、TCONS_l2_00021339 and NONHSAT104778 were positively correlated to stubborn(r=0.201~0.223, P<0.05); PR1~PR10 were positively correlated to aggressivity(r=0.207~0.259, P<0.05). 4. The scores of activation and aggressivity of NONHSAT021545 and NONHSAT041499 in high-expressed group were significantly lower than that in low-expressed group(P<0.05 or 0.01).

Conclusion

The abnormal expression of lncRNAs may have some relevance with schizophrenia, and to be specific, some lncRNAs may be associated with the positive and negative symptoms.

Key words: Schizophrenia, Long non-coding RNA, Biomarker, Positive and negative symptom scale

表1 芯片中筛查中差异表达的10种lncRNA

TargetID	FC (abs)	Regulation	P
NONHSAT021545	3.697919	up	0.023714
NONHSAT089447	3.514152	up	0.038920
NONHSAT098126	4.610542	up	0.047744

表1 芯片中筛查中差异表达的10种lncRNA

TargetID	FC (abs)	Regulation	P
NONHSAT021545	3.697919	up	0.023714
NONHSAT089447	3.514152	up	0.038920
NONHSAT098126	4.610542	up	0.047744

表2 病例组与对照组lncRNA比较(ΔCt±SD)

lncRNA	例数	PR1	PR2	PR3	PR4	PR5	PR6	PR7	PR8	PR9	PR10
病例组	96	4.14±4.28	5.03±4.72	5.21±4.95	4.23±4.79	3.60±4.57	4.51±4.56	5.05±3.98	5.80±4.82	3.75±4.87	5.67±4.80
对照组	44	5.73±4.43	6.50±5.11	6.83±5.38	6.28±5.37	5.31±4.65	6.48±4.50	6.70±4.45	7.50±5.33	5.55±5.33	4.76±5.10
Z值	?	－2.042	－1.571	－1.688	－2.038	－1.921	－2.177	－2.460	－1.742	－1.836	－1.737
P值	?	0.041	0.116	0.091	0.042	0.055	0.029	0.014	0.082	0.066	0.082

表2 病例组与对照组lncRNA比较(ΔCt±SD)

lncRNA	例数	PR1	PR2	PR3	PR4	PR5	PR6	PR7	PR8	PR9	PR10
病例组	96	4.14±4.28	5.03±4.72	5.21±4.95	4.23±4.79	3.60±4.57	4.51±4.56	5.05±3.98	5.80±4.82	3.75±4.87	5.67±4.80
对照组	44	5.73±4.43	6.50±5.11	6.83±5.38	6.28±5.37	5.31±4.65	6.48±4.50	6.70±4.45	7.50±5.33	5.55±5.33	4.76±5.10
Z值	?	－2.042	－1.571	－1.688	－2.038	－1.921	－2.177	－2.460	－1.742	－1.836	－1.737
P值	?	0.041	0.116	0.091	0.042	0.055	0.029	0.014	0.082	0.066	0.082

表3 病例组lncRNA与PANSS量表分的相关分析(n＝96)

lncRNA	阳性量表	阴性量表	一般病理量表	复合量表
ENST00000394742	0.244^a	－0.004	－0.006	0.000
TCONS_l2_00025502	0.276^b	－0.019	－0.023	0.014
NONHSAT098126	0.252^a	0.012	－0.026	－0.006
NONHSAT089447	0.258^a	－0.009	－0.018	0.030
ENST00000563823	0.257^a	0.011	－0.007	0.030
NONHSAT021545	0.249^a	－0.025	－0.027	0.008
NONHSAT041499	0.231^a	0.002	0.011	－0.041
ENST00000521622	0.247^a	0.007	0.020	0.028
TCONS_l2_00021339	0.260^a	0.009	0.002	0.055
NONHSAT104778	0.247^a	－0.007	－0.006	0.021

表3 病例组lncRNA与PANSS量表分的相关分析(n＝96)

lncRNA	阳性量表	阴性量表	一般病理量表	复合量表
ENST00000394742	0.244^a	－0.004	－0.006	0.000
TCONS_l2_00025502	0.276^b	－0.019	－0.023	0.014
NONHSAT098126	0.252^a	0.012	－0.026	－0.006
NONHSAT089447	0.258^a	－0.009	－0.018	0.030
ENST00000563823	0.257^a	0.011	－0.007	0.030
NONHSAT021545	0.249^a	－0.025	－0.027	0.008
NONHSAT041499	0.231^a	0.002	0.011	－0.041
ENST00000521622	0.247^a	0.007	0.020	0.028
TCONS_l2_00021339	0.260^a	0.009	0.002	0.055
NONHSAT104778	0.247^a	－0.007	－0.006	0.021

表4 病例组lncRNA与PANSS量表各症状群的相关分析(n＝96)

lncRNA	反应缺乏	思维障碍	激活性	偏执	抑郁	攻击性
PR1	0.025	0.059	0.289^b	0.190	-0.036	0.223^a
PR2	0.015	0.073	0.306^b	0.223^a	-0.080	0.229^a
PR3	0.056	0.024	0.352^b	0.198	-0.023	0.207^a
PR4	0.022	0.056	0.316^b	0.200	-0.077	0.236^a
PR5	0.037	0.049	0.316^b	0.206^a	-0.063	0.236^a
PR6	0.000	0.064	0.300^b	0.179	-0.044	0.211^a
PR7	0.031	0.088	0.243^a	0.162	-0.032	0.208^a
PR8	0.036	0.041	0.319^b	0.211^a	-0.044	0.250^a
PR9	0.042	0.048	0.327^b	0.218^a	-0.066	0.259^a
PR10	0.027	0.051	0.314^b	0.201^a	-0.066	0.238^a

表4 病例组lncRNA与PANSS量表各症状群的相关分析(n＝96)

lncRNA	反应缺乏	思维障碍	激活性	偏执	抑郁	攻击性
PR1	0.025	0.059	0.289^b	0.190	-0.036	0.223^a
PR2	0.015	0.073	0.306^b	0.223^a	-0.080	0.229^a
PR3	0.056	0.024	0.352^b	0.198	-0.023	0.207^a
PR4	0.022	0.056	0.316^b	0.200	-0.077	0.236^a
PR5	0.037	0.049	0.316^b	0.206^a	-0.063	0.236^a
PR6	0.000	0.064	0.300^b	0.179	-0.044	0.211^a
PR7	0.031	0.088	0.243^a	0.162	-0.032	0.208^a
PR8	0.036	0.041	0.319^b	0.211^a	-0.044	0.250^a
PR9	0.042	0.048	0.327^b	0.218^a	-0.066	0.259^a
PR10	0.027	0.051	0.314^b	0.201^a	-0.066	0.238^a

表5 病例组lncRNA高表达组和低表达组阳性、阴性症状的比较(±s)

因子	NONHSAT089447		t	P值	NONHSAT021545		t	P值	NONHSAT041499		t	P值
因子	高表达组	低表达组	t	P值	高表达组	低表达组	t	P值	高表达组	低表达组	t	P值
反应缺乏	10.48±3.65	10.85±2.92	0.51	0.0571	10.69±2.96	9.98±2.16	2.08	0.0613	10.13±2.78	10.62±3.61	1.87	0.0611
思维障碍	11.57±1.93	11.62±2.15	1.03	0.0611	10.48±2.48	11.05±1.79	1.51	0.0565	11.46±1.61	10.75±2.03	2.08	0.0573
激活性	7.42±1.80	8.18±2.97	2.05	0.0511	6.28±2.24	8.72±2.03	5.86	0.0091	5.46±1.90	8.14±2.23	4.88	0.0317
偏执	8.19±2.61	8.94±2.13	2.51	0.0607	7.83±2.72	8.23±1.98	2.64	0.0591	7.78±3.01	8.06±2.69	1.85	0.0721
抑郁	11.23±2.38	12.62±3.96	1.18	0.0513	11.62±3.52	11.69±2.96	0.83	0.0632	12.15±2.12	12.63±1.74	1.75	0.0833
攻击性	15.91±2.85	16.63±3.56	2.16	0.0564	16.75±3.13	20.39±4.01	5.12	0.0080	16.06±4.56	18.79±4.66	5.11	0.0090

表5 病例组lncRNA高表达组和低表达组阳性、阴性症状的比较(±s)

因子	NONHSAT089447		t	P值	NONHSAT021545		t	P值	NONHSAT041499		t	P值
因子	高表达组	低表达组	t	P值	高表达组	低表达组	t	P值	高表达组	低表达组	t	P值
反应缺乏	10.48±3.65	10.85±2.92	0.51	0.0571	10.69±2.96	9.98±2.16	2.08	0.0613	10.13±2.78	10.62±3.61	1.87	0.0611
思维障碍	11.57±1.93	11.62±2.15	1.03	0.0611	10.48±2.48	11.05±1.79	1.51	0.0565	11.46±1.61	10.75±2.03	2.08	0.0573
激活性	7.42±1.80	8.18±2.97	2.05	0.0511	6.28±2.24	8.72±2.03	5.86	0.0091	5.46±1.90	8.14±2.23	4.88	0.0317
偏执	8.19±2.61	8.94±2.13	2.51	0.0607	7.83±2.72	8.23±1.98	2.64	0.0591	7.78±3.01	8.06±2.69	1.85	0.0721
抑郁	11.23±2.38	12.62±3.96	1.18	0.0513	11.62±3.52	11.69±2.96	0.83	0.0632	12.15±2.12	12.63±1.74	1.75	0.0833
攻击性	15.91±2.85	16.63±3.56	2.16	0.0564	16.75±3.13	20.39±4.01	5.12	0.0080	16.06±4.56	18.79±4.66	5.11	0.0090

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A study on the relation of positive and negative symptoms to long non-coding RNAs with altered expressions in schizophrenia

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A study on the relation of positive and negative symptoms to long non-coding RNAs with altered expressions in schizophrenia