Systematic comparison of family history and polygenic risk across 24 common diseases

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Identification of cuproptosis‐related lncRNAs for prognosis and immunotherapy in glioma

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis‐related genes have prognostic predictive value has not been clarified. In this study, uni‐/multi‐variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis‐related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high‐ and low‐risk groups. Either for grade 2–3 or for grade 4, glioma patients with high‐risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high‐risk group was functionally associated with immune responses and cancer‐related pathways. The high‐risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high‐risk group were significantly higher than those in the low‐risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T‐cell co‐stimulation pathways. In conclusion, we established a risk model based on cuproptosis‐related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno‐microenvironment status of glioma.     

房颤射频消融术后复发风险预测评分系统的建立及评价

目的:探讨心房颤动(房颤)患者射频消融术后复发的风险因素,并依此构建个性化的风险评分系统。方法:选取2017年1~8月行射频消融术的房颤患者154例作为研究对象,依据术后3个月的随访结果将患者分为复发组及未复发组,采用单因素分析和Logistic回归分析对各风险因素进行分析,构建其评分系统,采用Hosmer-Lemeshow拟合优度检验和ROC曲线下面积评价评分系统的准确度及区分度。结果:术后随访3个月的结果显示共37例(24.03%)房颤患者出现复发,房颤类型、病程、体质量指数(BMI)、左房前后径(LAD)、左房容积(LAV)及超敏C反应蛋白(hs-CRP)水平均是房颤复发的独立风险因素(P<0.05)。构建的风险评分系统得分为0~26分,Hosmer-Lemeshow拟合优度检验:x^2=7.520,P=0.482;ROC曲线下面积为0.864(95%CI:0.837~0.891),预测评分值为15分时,约登指数最大(0.605),此时的敏感度和特异度分别为77.3%和83.2%。结论:房颤患者射频消融术后的复发率较高,依据风险因素构建的风险评分系统具有较高的预测效率和区分能力,可作为房颤患者射频消融术后复发风险评估的参考工具。     

Relationships between substance abuse/dependence and psychiatric disorders based on polygenic scores

Genetic susceptibility to substance use disorders (SUDs) is partially shared between substances. Heritability of any substance dependence, estimated as 54%, is partly explained by additive effects of common variants. Comorbidity between SUDs and other psychiatric disorders is frequent. The present study aims to analyze the additive role of common variants in this comorbidity using polygenic scores (PGSs) based on genome‐wide association study discovery samples of schizophrenia (SCZ), bipolar disorder, attention‐deficit/hyperactivity disorder, autism spectrum disorder, major depressive disorder and anxiety disorders, available from large consortia. PGSs were calculated for 534 patients meeting DSM‐IV criteria for dependence of a substance and abuse/dependence of another substance between alcohol, tobacco, cannabis, cocaine, opiates, hypnotics, stimulants, hallucinogens and solvents; and 587 blood donors from the same population, Iberians from Galicia, as controls. Significance of the PGS and percentage of variance explained were calculated by logistic regression. Using discovery samples of similar size, significant associations with SUDs were detected for SCZ PGS. SCZ PGS explained more variance in SUDs than in most psychiatric disorders. Cross‐disorder PGS based on five psychiatric disorders was significant after adjustment for the effect of SCZ PGS. SCZ PGS was significantly higher in women than in men abusing alcohol. Our findings indicate that SUDs share genetic susceptibility with SCZ to a greater extent than with other psychiatric disorders, including externalizing disorders such as attention‐deficit/hyperactivity disorder. Women have lower probability to develop substance abuse/dependence than men at similar PGS probably because of a higher social pressure against excessive drug use in women.     

Circulating exosome‐derived bona fide long non‐coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma

Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell‐free plasma was applied. The risk score analysis was employed to screen the potential exosome‐derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi‐stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer‐free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer‐free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.     

Integrated analysis of gene expression and DNA methylation datasets identified key genes and a 6-gene prognostic signature for primary lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the main subtype of non-small cell lung cancer with a poor survival prognosis. In our study, gene expression, DNA methylation, and clinicopathological data of primary LUAD were utilized to identify potential prognostic markers for LUAD, which were recruited from The Cancer Genome Atlas (TCGA) database. Univariate regression analysis showed that there were 21 methylation-associated DEGs related to overall survival (OS), including 9 down- and 12 up-regulated genes. The 12 up-regulated genes with hypomethylation may be risky genes, whereas the other 9 down-regulated genes with hypermethylation might be protective genes. By using the Step-wise multivariate Cox analysis, a methylation-associated 6-gene (consisting of CCL20, F2, GNPNAT1, NT5E, B3GALT2, and VSIG2) prognostic signature was constructed and the risk score based on this gene signature classified patients into high- or low-risk groups. Patients of the high-risk group had shorter OS than those of the low-risk group in both the training and validation cohort. Multivariate Cox analysis and the stratified analysis revealed that the risk score was an independent prognostic factor for LUAD patients. The methylation-associated gene signature may serve as a prognostic factor for LUAD patients and the represent hypermethylated or hypomethylated genes might be potential targets for LUAD therapy.     

Prognosis and clinical features analysis of EMT-related signature and tumor Immune microenvironment in glioma

BackgroundAs the most common primary malignant intracranial tumor, glioblastoma has a poor prognosis with limited treatment options. It has a high propensity for recurrence, invasion, and poor immune prognosis due to the complex tumor microenvironment.MethodsSix groups of samples from four datasets were included in this study. We used consensus ClusterPlus to establish two subgroups by the EMT-related gene. The difference in clinicopathological features, genomic characteristics, immune infiltration, treatment response and prognoses were evaluated by multiple algorithms. By using LASSO regression, multi-factor Cox analysis, stepAIC method, a prognostic risk model was constructed based on the final screened genes.ResultsThe consensusClusterPlus analyses revealed two subtypes of glioblastoma (C1 and C2), which were characterized by different EMT-related gene expression patterns. C2 subtype with the worse prognosis had the more malignant clinical and pathology manifestations, higher Immune infiltration and tumor-associated molecular pathways scores, and poorer response to treatment. Additionally, our EMT-related genes risk prediction model can provide valuable support for clinical evaluations of glioma.ConclusionsThe assessment system and prediction model displayed good performance in independent prognostic risk assessment and individual patient treatment response prediction. This can help with clinical treatment decisions and the development of effective treatments.     

NRS2002评分和血清白蛋白值与门诊肺结核患者病情的相关性

目的 评价NRS2002评分和血清白蛋白（ALB）值与门诊肺结核患者病情的相关性。 方法 选择2017年10月至2018年9月在余姚市人民医院肺结核门诊就诊的290名肺结核患者为研究对象。患者首次就诊时进行NRS2002营养筛查,NRS2002评分≥3分判定为存在营养风险。检测患者血清白蛋白（ALB）值,ALB≤35 g/L判定为营养不足。观察患者NRS2002评分、ALB值与肺结核患者痰液结核分枝杆菌阳性、肺结核空洞等情况的相关性。 结果 NRS2002评分、年龄与肺结核患者的病情相关。NRS2002评分≥3分以及ALB≤35 g/L的患者痰液结核分枝杆菌阳性率和存在肺结核空洞的比例均高于NRS2002评分35 g/L的患者（均P40岁为肺结核患者痰液结核分枝杆菌阳性的危险因素;而年龄、性别、NRS2002评分和ALB值均不是患者肺结核空洞的危险因素。 结论 NRS2002评分≥3分、ALB≤35 g/L的肺结核患者更容易出现痰液结核分枝杆菌阳性情况。肺结核患者营养状况与肺结核患者病情具有一定相关性。     

E-PASS评分系统用于评估老龄患者消化道手术后并发症和转归的临床价值研究

目的:评价日常活动和手术应激评估(Estimation of physiologic ability and surgical stress,E-PASS)系统用于评估老龄患者消化道手术后并发症和转归的临床价值。方法:回顾性分析2011年7月至2013年7月西京医院消化外科所有65岁以上的患者的临床资料,计算其中行消化道手术者的E-PASS评分,并记录这些患者术后并发症的发生情况和患者术后的住院时间。分析E-PASS评分和几项该评分未涉及的因素与老龄患者消化道手术后并发症的发病率、死亡率、住院时间的相关性。结果:研究共纳入1236例老龄行消化道手术的患者,其中521例发生术后并发症(42.15%),8例死亡(0.65%)。患者术前E-PASS评分系统中,三项评分均与术后住院时间相关,术前风险评分(Preoperative risk score,PRS)和综合风险评分(Comprehensive risk score,CRS)与术后并发症的发病率和死亡率显著相关(P均0.05)。E-PASS评分系统未包含的指标中,麻醉方法与术后并发症发生和住院时间无关,术后入ICU、术中使用血管活性药物和急诊手术与术后发病率、死亡率和住院时间相关(P均0.05)。结论:E-PASS评分系统可用于预测老龄患者行消化道手术后并发症的发生情况和转归,纳入术后入ICU、术中使用血管活性药物和急诊手术三项指标可能进一步提高E-PASS评分系统的预测准确性。     

Developing a risk scoring system based on immune-related lncRNAs for patients with gastric cancer

The immune system and the tumor interact closely during tumor development. Aberrantly expressed long non-coding RNAs (lncRNAs) may be potentially applied as diagnostic and prognostic markers for gastric cancer (GC). At present, the diagnosis and treatment of GC patients remain a formidable clinical challenge. The present study aimed to build a risk scoring system to improve the prognosis of GC patients. In the present study, ssGSEA was used to evaluate the infiltration of immune cells in GC tumor tissue samples, and the samples were split into a high immune cell infiltration group and a low immune cell infiltration group. About 1262 differentially expressed lncRNAs between the high immune cell infiltration group and the low immune cell infiltration group. About 3204 differentially expressed lncRNAs between GC tumor tissues and paracancerous tissues were identified. Then, 621 immune-related lncRNAs were screened using a Venn analysis based on the above results, and 85 prognostic lncRNAs were identified using a univariate Cox analysis. We constructed a prognostic signature using LASSO analysis and evaluated the predictive performance of the signature using ROC analysis. GO and KEGG enrichment analyses were performed on the lncRNAs using the R package, ‘clusterProfiler’. The TIMER online database was used to analyze correlations between the risk score and the abundances of the six types of immune cells. In conclusion, our study found that specific immune-related lncRNAs were clinically significant. These lncRNAs were used to construct a reliable prognostic signature and analyzed immune infiltrates, which may assist clinicians in developing individualized treatment strategies for GC patients.     

Rockall危险性积分对急性上消化道出血患者临床预后的预测价值

目的:探讨Rockall危险性积分对急性上消化道出血(AUGIH)患者临床预后的预测价值。方法:选择2012年1月至2014年1月我院收治的120例AUGIH患者,依据Rockall评分标准对患者相关临床资料进行收集,并计算其Rockall危险性积分评分,记录患者再出血率及死亡率。结果:120例AUGIH患者中,低危组39例(32.5%)、中危组72例(60.0%)、高危组9例(7.5%)。高危组患者再出血率及死亡率分别为33.3%和22.2%,均明显高于中危组16.7%和15.3%,比较差异具有统计学意义(P0.05)。结论:Rockall评分系统可作为AUGIH患者预后预测的重要指标,对急诊AUGIH预后的判断具有重要临床意义。     

Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

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遗传风险评分在复杂疾病遗传学研究中的应用

心血管疾病、2型糖尿病、原发性高血压、哮喘、肥胖、肿瘤等复杂疾病在全球范围内流行,并成为人类死亡的主要原因。越来越多的人开始关注遗传易感性在复杂疾病发病机制中的作用。至今,与复杂疾病相关的易感基因和基因序列变异仍未完全清楚。人们希望通过遗传关联研究来阐明复杂疾病的遗传基础。近年来,全基因组关联研究和候选基因研究发现了大量与复杂疾病有关的基因序列变异。这些与复杂疾病有因果和(或)关联关系的基因序列变异的发现促进了复杂疾病预测和防治方法的产生和发展。遗传风险评分(Genetic risk score,GRS)作为探索单核苷酸多态(Single nucleotide polymorphisms,SNPs)与复杂疾病临床表型之间关系的新兴方法,综合了若干SNPs的微弱效应,使基因多态对疾病的预测性大幅度提升。该方法在许多复杂疾病遗传学研究中得到成功应用。本文重点介绍了GRS的计算方法和评价标准,简要列举了运用GRS取得的系列成果,并对运用过程中所存在的局限性进行了探讨,最后对遗传风险评分的未来发展方向进行了展望。