WO2022022060A1 - Mci诊断标志物、mci诊断试剂盒及相应的检测方法 - Google Patents
Mci诊断标志物、mci诊断试剂盒及相应的检测方法 Download PDFInfo
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Definitions
- the invention relates to the technical field of the prodromal stage of Alzheimer's disease, in particular to the technical field of diagnostic markers, in particular to a diagnostic marker for mild cognitive impairment and an application thereof.
- AD Alzheimer's disease
- a variety of neuropsychiatric symptoms and behavioral abnormalities, the main pathological features are senile plaques formed by the deposition of extracellular amyloid and cerebral cortical neurons caused by neurofibrillary tangles formed by the hyperphosphorylation of microtubule-related Tau protein in neurons apoptosis.
- the incidence of Alzheimer's disease is increasing year by year.
- the annual report on Alzheimer's disease in the world there is a new dementia patient every 3 seconds, and the number of patients has reached 50 million. It is expected that this number will reach 50 million. It will reach 152 million in 2050.
- Mild cognitive impairment is a transitional state of cognitive function between normal aging and dementia.
- MCI is divided into two subtypes: amnestic MCI and non-amnestic MCI.
- amnestic MCI is increasingly considered to be the prodromal stage of AD.
- Studies have shown that approximately 10-15% of patients with amnestic MCI progress to probable AD each year.
- MCI is a high-risk group that needs intervention, and it is also the best entry point for early preventive intervention. In the past 20 years, the diagnostic research of AD and MCI has made great progress.
- AD and MCI are mainly through the consultation of professional doctors, judged according to the medical history and scale scores, mainly the Montreal Cognitive Assessment Scale, the complete set of neuropsychological tests, the Simple Mental State Scale and the Clinical Dementia Scale, etc. , but the evaluation of the scale is time-consuming, labor-intensive, and relatively inaccurate.
- Auxiliary examinations mainly include brain structure imaging examination, which can observe the macroscopic changes of the patient's brain structure, but cannot detect early characteristic changes, especially MCI.
- Senile plaque imaging detection as the current gold standard for AD diagnosis, can detect pathological changes, but it is expensive and has no clinical application in China. Therefore, there is no clinical method for early diagnosis of clinical biomarkers that can be promoted and applied clinically in China. Exploring the use of peripheral blood biomarkers to screen potential MCI patients will help in the early diagnosis and treatment of AD.
- lncRNA Long non-coding RNA
- LncRNA is not only abundant in brain tissue, but also stably exists in cerebrospinal fluid, plasma and serum samples. Among the biological samples of human biology, peripheral blood samples are the easiest to obtain, the ones that are simple to operate, the least traumatic, and the ones that patients bear the least risk and pain.
- Blood is considered to be the most suitable biological sample for screening AD high-risk groups for early detection, diagnosis, and follow-up of therapeutic interventions for AD.
- the structural features of lncRNA endow it with the ability to be detected free from the enzymatic activity of endogenous RNases and to be a stable diagnostic plasma biomarker for MCI and AD.
- the lncRNA research results provided by the applicant suggest that the expression of several genetic markers in peripheral blood lncRNA is different between MCI and normal controls.
- the detection of plasma lncRNA expression level can be used as a routine method for screening early diagnosis of AD, optimizing clinical Diagnostic strategies for AD.
- the purpose of the present invention is to overcome the above-mentioned shortcomings of the prior art, and to provide a diagnostic marker for mild cognitive impairment that can effectively screen for early diagnosis of AD and optimize clinical AD diagnosis strategy and its application.
- one aspect of the present invention provides a diagnostic marker for mild cognitive impairment (MCI), which has the following composition:
- the marker is plasma lncRNA, and the plasma lncRNA includes one or more of ENST00000549762, NR_024049, T324988 or ENST00000567919.
- the present invention also provides an application of the mild cognitive impairment diagnostic marker in the preparation of a mild cognitive impairment diagnostic kit.
- the present invention also provides a mild cognitive impairment diagnostic kit, which measures the content of one or more of ENST00000549762, NR_024049, T324988 or ENST00000567919 in plasma.
- the kit includes one or more primers and probes of ENST00000549762, NR_024049, T324988 or ENST00000567919.
- the kit contains the internal reference 18S.
- the calculation formula brought in by the content of one or more of ENST00000549762, NR_024049, T324988 or ENST00000567919 in the plasma measured by the kit is:
- the present invention also provides a method for detecting MCI diagnostic markers based on the mild cognitive impairment diagnostic kit, the method comprising the steps of:
- the total RNA to be detected is subjected to reverse transcription reaction using a lncRNA reverse transcription kit to obtain the corresponding cDNA;
- the beneficial effects of the present invention are: through rigorous experiments and statistical analysis, four nucleic acid molecules of biomarkers ENST00000549762, NR_024049, T324988 and ENST00000567919, which have high diagnostic value for amnestic mild cognitive impairment, are discovered for the first time.
- biomarkers ENST00000549762, NR_024049, T324988 and ENST00000567919 which have high diagnostic value for amnestic mild cognitive impairment
- Fig. 1 is a flow chart of the experimental design of the screening, training and validation of the combined chip for identifying the plasma target lncRNA of MCI patients according to the present invention.
- Fig. 2 is a diagram showing the main steps of the method for determining the plasma lncRNA composition of the diagnosis of MCI patients of the present invention.
- Figure 3 shows the ROC curves of the four lncRNA combinations used to diagnose MCI patients.
- Figure 4 shows the ROC curves of the three lncRNA combinations in the diagnosis of MCI patients.
- Figure 5 shows the ROC curve of using a combination of lncRNAs to diagnose MCI patients.
- the subjects were 50 elderly patients with MCI collected from the community in Xuhui District, Shanghai, and the control group was healthy elderly matched for age, gender, and educational age.
- the lncRNA was labeled with the Arraystar RNA Flash Labeling Kit. After labeling, the samples were hybridized to the Array human lncRNA chip (v4.0) using Agilent SureHyb in a total reaction volume of 50 ⁇ l.
- Chip signal values were acquired using Agilent Feature Extraction software.
- the Agilent GeneSpring GX v12.1 software was used for chip normalization and screening for differentially expressed lncRNAs.
- the lncRNAs that were significantly up-regulated in the control group were selected for real-time quantitative PCR verification.
- the specific implementation methods are as follows:
- the total reaction volume is 20ul (total RNA 300ng, reverse transcription specific primer 1 ⁇ l, dNTP 1.6 ⁇ l, add nuclease-free water to 13.5 ⁇ l, then add RNA inhibitor 0.5 ⁇ l, reverse transcriptase 1 ⁇ l, buffer 4 ⁇ l, 0.1M DTT 1 ⁇ l) , at different temperatures (50°C, 70°C) for different durations (60 minutes, 15 minutes) reactions.
- ROC curve analysis showed that four lncRNAs, NST00000567919, ENST00000549762, NR_024049, and T324988, had high diagnostic value for MCI as biomarkers.
- the above four lncRNAs are independent variables, and the four lncRNAs are individually or jointly predicted as dependent variables. Logistic binomial regression is performed to calculate the predicted probability value.
- the calculation models (calculation model 1, calculation model 2, calculation model 3, calculation model The values obtained from model 4, calculation model 5, calculation model 6, calculation model 7, calculation model 8, and calculation model 9) were subjected to ROC curve analysis again, and the results showed that the numerical values obtained by the calculation model still had high diagnostic value.
- the calculation model 1 is:
- the AUC was 0.941, the cutoff value was -0.8392, the sensitivity was 92%, and the specificity was 84%.
- the calculation model 2 is:
- the AUC was 0.935, the cutoff value was -0.6984, the sensitivity was 88%, and the specificity was 84%.
- the calculation model 3 is:
- the AUC was 0.926, the cutoff value was -0.5859, the sensitivity was 90%, and the specificity was 84%.
- the calculation model 4 is:
- the AUC was 0.920, the cutoff value was -0.3367, the sensitivity was 88%, and the specificity was 84%.
- the calculation model 5 is:
- the AUC was 0.930, the cutoff value was -0.2550, the sensitivity was 90%, and the specificity was 90%.
- the calculation model 6 is:
- the AUC was 0.846, the cutoff value was 0.000160542039, the sensitivity was 80%, and the specificity was 80%.
- the calculation model 7 is:
- the AUC was 0.877, the cutoff value was 0.000235892192, the sensitivity was 82%, and the specificity was 86%.
- the calculation model 8 is:
- the AUC was 0.900, the cutoff value was 0.243255710000, the sensitivity was 92%, and the specificity was 82%.
- the calculation model 9 is:
- the AUC was 0.856, the cutoff value was 0.000502313314, the sensitivity was 82%, and the specificity was 80%.
- the beneficial effects of the present invention are: through extensive literature reading and review, through rigorous experiments and statistical analysis, four nucleic acid molecules of biomarkers NST00000567919, ENST00000549762, NR_024049 and T324988 with high diagnostic value for MCI are discovered for the first time.
- the dilemma of no convenient MCI peripheral plasma diagnostic markers has been broken through, which is beneficial to the early diagnosis and early intervention of Alzheimer's disease.
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Abstract
Description
Claims (7)
- 一种MCI诊断标志物,其特征在于,所述的标志物为血浆lncRNA,所述的血浆lncRNA包括ENST00000549762、NR_024049、T324988或ENST00000567919中的一种或多种。
- 一种权利要求1所述的MCI诊断标志物在制备MCI诊断试剂盒中的应用。
- 一种MCI诊断试剂盒,其特征在于,所述的试剂盒测定血浆中的ENST00000549762、NR_024049、T324988或ENST00000567919中的一种或多种的含量。
- 根据权利要求3所述的MCI诊断试剂盒,其特征在于,所述的试剂盒中包括的ENST00000549762、NR_024049、T324988或ENST00000567919中的一种或多种的引物和探针。
- 根据权利要求3所述MCI诊断试剂盒,其特征在于,所述的试剂盒所中含有内参18S。
- 根据权利要求3所述的MCI诊断试剂盒,其特征在于,所述的试剂盒所测定血浆中的ENST00000549762、NR_024049、T324988或ENST00000567919中的一种或多种的含量带入的计算公式为:(1)-4.749+7972.194×ENST00000549762+5609.072×NR_024049+5.073×T324988+961.747×ENST00000567919;(2)-4.628+8552.604×ENST00000549762+5885.819×NR_024049+6.017×T324988;(3)-4.549+9376.777×ENST00000549762+6908.534×NR_024049+2195.991×ENST00000567919;(4)-4.220+6823.570×NR_024049+5.849×T324988+1213.731×ENST00000567919;(5)-4.129+6.122×T324988+1128.888×ENST00000567919+9678.308×ENST00000549762;(6)ENST00000549762;(7)NR_024049;(8)T324988;或者,(9)ENST00000567919。
- 一种基于权利要求3至6中任一项所述MCI诊断试剂盒进行MCI诊断标志物检测的方法,其特征在于,所述的方法包括步骤:(1)将待检测的总RNA使用lncRNA逆转录试剂盒进行逆转录反应,得到相应的cDNA;(2)将得到的cDNA进行实时荧光定量PCR,并以18S为内参,检测结果以ΔCt表示,其中ΔCt=Ct lncRNA-Ct 18S;(3)将得到的ΔCt结果带入以下公式中:-4.749+7972.194×ENST00000549762+5609.072×NR_024049+5.073×T324988+961.747×ENST00000567919;-4.628+8552.604×ENST00000549762+5885.819×NR_024049+6.017×T324988;-4.549+9376.777×ENST00000549762+6908.534×NR_024049+2195.991×ENST00000567919;-4.220+6823.570×NR_024049+5.849×T324988+1213.731×ENST00000567919;-4.129+6.122×T324988+1128.888×ENST00000567919+9678.308×ENST00000549762;ENST00000549762;NR_024049;T324988;或者,ENST00000567919。
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CN113667737A (zh) * | 2020-07-31 | 2021-11-19 | 上海市精神卫生中心(上海市心理咨询培训中心) | Mci诊断标志物、mci诊断试剂盒及相应的检测方法 |
CN113234812B (zh) * | 2021-06-09 | 2023-11-03 | 科德角国际生物医学科技(北京)有限公司 | 一种用于诊断阿尔茨海默病的诊断试剂 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106978507A (zh) * | 2017-06-07 | 2017-07-25 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAsENST00000508241、试剂盒及应用 |
CN108866182A (zh) * | 2018-08-21 | 2018-11-23 | 孔祥东 | 长链非编码rna作为阿尔茨海默病检测标志物的应用 |
WO2020049135A1 (en) * | 2018-09-05 | 2020-03-12 | Amoneta Diagnostics Sas | Long non-coding rnas (lncrnas) for the diagnosis and therapeutics of brain disorders, in particular cognitive disorders |
CN111373052A (zh) * | 2017-09-05 | 2020-07-03 | 阿莫内塔诊断公司 | 非编码RNA(ncRNA)用于认知障碍的诊断 |
CN111690739A (zh) * | 2020-07-31 | 2020-09-22 | 上海市精神卫生中心(上海市心理咨询培训中心) | Mci诊断标志物、mci诊断试剂盒及相应的检测方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10169530B2 (en) * | 2012-11-05 | 2019-01-01 | Genomic Health, Inc. | Gene fusions and alternatively spliced junctions associated with breast cancer |
CN108823305B (zh) * | 2017-04-28 | 2021-08-13 | 青岛市中心医院 | 一种同步检测8种肿瘤相关长链非编码rna的多重pcr方法 |
CN109055541B (zh) * | 2018-09-26 | 2020-08-28 | 上海市精神卫生中心(上海市心理咨询培训中心) | Ad所致mci诊断标志物及其应用 |
-
2020
- 2020-07-31 CN CN202110966071.7A patent/CN113667737A/zh active Pending
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106978507A (zh) * | 2017-06-07 | 2017-07-25 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAsENST00000508241、试剂盒及应用 |
CN111373052A (zh) * | 2017-09-05 | 2020-07-03 | 阿莫内塔诊断公司 | 非编码RNA(ncRNA)用于认知障碍的诊断 |
CN108866182A (zh) * | 2018-08-21 | 2018-11-23 | 孔祥东 | 长链非编码rna作为阿尔茨海默病检测标志物的应用 |
WO2020049135A1 (en) * | 2018-09-05 | 2020-03-12 | Amoneta Diagnostics Sas | Long non-coding rnas (lncrnas) for the diagnosis and therapeutics of brain disorders, in particular cognitive disorders |
CN111690739A (zh) * | 2020-07-31 | 2020-09-22 | 上海市精神卫生中心(上海市心理咨询培训中心) | Mci诊断标志物、mci诊断试剂盒及相应的检测方法 |
Non-Patent Citations (2)
Title |
---|
See also references of EP4190899A4 |
SEREBROVSKA ZOYA O., SEREBROVSKA TETIANA V., KHOLIN VIKTOR A., TUMANOVSKA LESYA V., SHYSH ANGELA M., PASHEVIN DENIS A., GONCHAROV : "Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL (MDPI), BASEL, CH, vol. 20, no. 21, 5405, 1 November 2019 (2019-11-01), Basel, CH , pages 5405 - 17, XP055893631, ISSN: 1661-6596, DOI: 10.3390/ijms20215405 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114736959A (zh) * | 2022-05-09 | 2022-07-12 | 上海市精神卫生中心(上海市心理咨询培训中心) | 轻度认知功能损害诊断标志物、试剂盒及其应用 |
CN114736959B (zh) * | 2022-05-09 | 2023-09-22 | 上海市精神卫生中心(上海市心理咨询培训中心) | 轻度认知功能损害诊断标志物、试剂盒及其应用 |
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