急性早幼粒细胞白血病预后生存模型的建立

目的分析影响急性早幼粒细胞白血病(APL)预后的危险因素,并以多参数指标建立APL患者的预后生存模型。方法选取2013年7月—2017年7月浙江大学医学院附属第一医院218例APL患者作为研究对象,将患者分为早期死亡组(18例)和非早期死亡组(200例),分析影响APL预后的危险因素,并建立预后生存模型。结果年龄>60岁、白细胞(WBC)计数>10×10~9/L、纤维蛋白原(Fib)≤1.4 g/L、血清肌酐(SCr)>105μmol/L、血清乳酸脱氢酶(LDH)>250 U/L、早幼粒细胞白血病-维甲酸受体α(PML-RARa)融合基因SG阳性与APL患者早期死亡密切相关(P<0.05);多因素Logistic回归分析发现,年龄[比值比(OR)=1.049,95%可信区间(CI)为1.003~1.098,P=0.038]和WBC计数(OR=1.030,95%CI为1.007~1.054,P=0.012)为APL患者预后的独立危险因素;预后生存模型根据初诊时APL患者年龄、WBC计数、Fib、LDH、SCr、PML-RARa融合基因亚型6项指标建立,其受试者工作特征(ROC)曲线的曲线下面积(AUC)为0.797,敏感性为71.4%,特异性为92.6%。结论年龄、WBC计数为APL预后的独立危险因素,所建立的预后生存模型对预测患者生存状态有重要意义。

基于贝叶斯网络构建晚期非小细胞肺癌生存预后模型

根据我国最新发布的全国癌症报告,无论是发病率还是死亡率,肺癌均居于所有恶性肿瘤之首,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占所有肺癌病例的80%左右。根据2020年美国癌症协会发布的统计数据,高达57%的肺癌患者诊断时即为晚期,其5年生存率仅5.8%^([1])。因此,建立可信度高、预测效果好的NSCLC预后预测评估模型,对于患者的个体化治疗、临床医师决策制定以及社会医疗资源的合理利用具有重要的指导意义。本研究通过大量文献阅读整理出可能有预测作用的因素,聚焦炎症指标、肿瘤指标、营养学指标这三方面血液学常规指标,利用贝叶斯网络模型建立一项经济实用、预测效果好的NSCLC预后预测模型,为患者最终治疗方案的选择和预后的判断提供决策支持。

m5C甲基化相关基因预测肾透明细胞癌的预后

目的:利用肿瘤基因组图谱(the Cancer Genome Atlas,TCGA)数据库中的数据,构建m5C甲基化相关基因组成的生存预后模型,分析与肾透明细胞癌生存有关的独立预后影响因素以预测肾透明细胞癌患者的预后。方法:从TCGA数据库下载肾透明细胞癌患者资料,从已发表的文献中获取m5C甲基化相关基因并分析其在肿瘤组和对照组间的表达差异。对这些基因进行共识聚类分析以揭示m5C甲基化相关基因与肾透明细胞癌预后之间的关系。通过单变量Cox分析和Lasso-Cox回归分析构建出生存预后模型并分析与肾透明细胞癌相关的预后影响因素,GO和KEGG富集分析进一步探索生物功能和潜在的信号通路。通过qRT-PCR验证m5C甲基化相关基因在肾透明细胞癌细胞系及组织和正常肾细胞系及组织之间的差异表达。结果:m5C甲基化相关基因在肾透明细胞癌肿瘤组和正常组之间存在差异性表达。共识聚类分析结果显示亚群1的肾透明细胞癌患者预后优于亚群2。构建的生存预后模型将肾透明细胞癌分为高风险组和低风险组,单变量和多变量Cox分析显示分级和分期可能是肾透明细胞癌的独立预后因素,而GO和KEGG分析显示m5C-RNA甲基化修饰可影响肾透明细胞癌的进展。此外,qRT-PCR实验也证实m5C甲基化相关基因在肾透明细胞癌肿瘤组和正常组之间表达存在差异。结论:本文构建的m5C甲基化相关基因的生存预后模型可以预测肾透明细胞癌患者的预后。

自噬相关标志物对子宫内膜癌患者生存预后的预测价值及对化疗效果的影响

目的探讨自噬凋亡在子宫内膜癌(UCEC)中的潜在机制,分析自噬凋亡对生存预后的影响。方法基因组测序数据来自癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和基因型组织表达(Genotype-Tissue Expression,GTEx)数据库,筛选获得UCEC相关的差异表达基因及UCEC生存预后相关的关键自噬基因,然后构建并验证UCEC患者生存预后的风险评分预测模型,分析自噬凋亡对UCEC生存预后的影响。结果共筛选出1964个差异表达基因,包含631个(32.13%)上调基因、1333个(67.87%)下调基因,其中21个子宫内膜癌相关自噬差异表达基因(UCEC-AT-DEGs)。Kaplan-Meier生存分析结果显示,EIF4EBP1、CDKN2A、VEGFA基因的表达升高,均导致UCEC总生存期缩短(均P<0.05)。决策树分析(DCA)曲线显示:EIF4EBP1对UCEC的2年、3年生存率影响具有较高的临床应用价值。LASSO回归结果显示,风险评分Riskscore=0.1395×EIF4EBP1+0.1827×CDKN2A+0.0791×ITPR1+0.2658×GRID1-0.0187×TM9SF1-0.1250×RAB24+0.0710×VEGFA(λ_(min)=0.0172),该模型具有可靠的预测性能。EIF4EBP1表达水平与顺铂的半数最大抑制浓度(IC50)呈负相关,CDKN2A表达水平与紫杉醇和顺铂的IC50均呈负相关(均P<0.05)。结论多个自噬基因在UCEC中的表达变化明显,部分关键自噬基因的异常高表达对UCEC患者的总生存率产生不良影响;EIF4EBP1、CDKN2A对UCEC的2年、3年生存率影响具有较高的临床应用价值,并对一线化疗药物的效果产生一定影响。

Comparison scoring model of severe viral hepatitis and model of end stage liver disease for the prognosis of patients with liver failure in China

AIM:To estimate the prognosis of patients with liver failure using a scoring model of severe viral hepatitis (SMSVH) and a model of end stage liver disease (MELD) to provide a scientific basis for clinical decision of treatment. METHODS:One hundred and twenty patients with liver failure due to severe viral hepatitis were investigated with SMSVH established. Patients with acute,subacute,and chronic liver failure were 40,46 and 34,respectively. The follow-up time was 6 mo. The survival rates of patients with liver failure in 2 wk,4 wk,3 mo and 6 mo were estimated with Kaplan-Meier method. Comparison between SMSVH and MELD was made using ROC statistic analysis. RESULTS:The survival curves of group A (at low risk,SMSVH score ≤ 4) and group B (at high risk,SMSVH score ≥ 5) were significantly different (The 4-wk,3-mo,6-mo survival rates were 94.59%,54.05%,43.24% in group A,and 51.81%,20.48%,12.05% in group B,respectively,P < 0.001). The survival curves of group C (SMSVH scores unchanged or increased),group D (SMSVH scores decreased by 1) and group E (SMSVH scores decreased by 2 or more) were significantly different .The survival rates of groups C,D and E were 66.15%,100%,100% in 2-wk; 40.0%,91.18%,100% in 4-wk; 0%,58.82%,80.95% in 3-mo and 0%,38.24%,61.90% in 6-mo,respectively,P < 0.001). The area under the ROC curve (AUC) of SMSVH scores at baseline and after 2 wk of therapy was significantly higher than that under the ROC curve of MELD scores (0.804 and 0.934 vs 0.689,P < 0.001). CONCLUSION:SMSVH is superior to MELD in theestimation of the prognosis of patients with severe viral hepatitis within 6 mo. SMSVH may be regarded as a criterion for estimation of the efficacy of medical treatment and the decision of clinical treatment.

生物信息学分析肾透明细胞癌中NLR信号通路的作用和临床意义

目的探讨寡聚化核苷酸结合结构域样受体(nucleotide-binding structural domain-like receptor,NLR)信号通路在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的作用和临床意义,为寻找新靶点提供参考。方法从癌症基因组图谱(The Cancer GenomeAtlas,TCGA)、基因表达综合(gene expression omnibus,GEO)、ArrayExpress和GEPAI2.0等数据库中下载ccRCC相关数据,利用R软件分析NLR信号通路在正常组织和癌组织中的富集差异,及其与T、N、M、肿瘤分级和分期等临床指标间的相关性,进一步分析该通路与ccRCC患者预后的关系,单细胞测序数据用于聚类和基因表达分析,通过免疫逃逸相关的基因集富集分析(genesetenrichmentanalysis,GSEA)和相关分析研究免疫与通路的关系,用免疫治疗数据进行生存分析和构建免疫相关生存预后模型。结果NLR信号通路在ccRCC中异常富集(P<0.05),其富集趋势与各临床指标趋势相同,高富集该信号通路与不良预后有关(P<0.05),上调NLR信号通路与下调NK细胞、M1巨噬细胞,上调中性粒细胞、巨噬细胞等免疫细胞浸润水平相关,同时分析表明该通路与免疫逃逸间存在相互作用,基于11个差异基因构建的免疫治疗生存预后模型预测患者1年、3年、5年生存率的受试者工作特征曲线曲线下面积分别为0.64、0.69、0.75。结论NLR信号通路是ccRCC的关键生物途径,与免疫逃逸之间的窜扰促使ccRCC发生、发展,11个NLR通路相关基因成功构建免疫疗法的生存预后模型,免疫疗法中它们可能是预后生物标志物和潜在治疗靶点。

Prognostic factors for 5-year survival after local excision of rectal cancer

AIM:To evaluate the prognostic factors for 5-year survival after local excision of rectal cancer,and to examine the therapeutic efficacy and surgical indications for this procedure. METHODS:Clinical data,obtained from 106 local rectal cancer excisions performed between January 1980 and December 2005,were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier method,statistical comparisons were performed using the log-rank test,and multivariate analysis was performed using the Cox proportional hazards model. RESULTS:Transanal,transsacral,and transvaginal excisions were performed in 92,12,and 2 cases, respectively.The rate of complication,local recurrence, and 5-year survival was 6.6%,17.0%,and 86.7%, respectively.Univariate analysis showed that T stage, vascular invasion,and local recurrence were related to the prognosis of the cases(P<0.05).Multivariate analysis showed that T stage[P=0.011,95% confidence interval(CI)=1.194-3.878]and local recurrence(P=0.022,95%CI=1.194-10.160)were the major prognostic factors for 5-year survival of cases after local excision of rectal cancer. CONCLUSION:Local rectal cancer excision is associated with few complications,and suitable for stages Tis and T1 rectal cancer.Prevention of local recurrence,active postoperative follow-up,and administration of salvage therapy are the effective methods to increase the efficacy of local excision of rectal cancer.