TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer

BackgroundColon cancer is one of the most common malignant tumors, with high rates of incidence and death. The tumor mutational burden (TMB), which is characterized by microsatellite instability, has been becoming a powerful predictor which can show tumor behavior and response to immunotherapy.MethodsIn this study, we analyzed 437 mutation data of colon cancer samples obtained from The Cancer Genome Atlas (TCGA) and divided patients into low- and high-TMB groups according to the TMB value. Then we identified differentially-expressed genes (DEGs), conducted immune cell infiltration and survival analyses between groups.ResultsThe higher TMB of the patients with colon cancer predicts a poorer prognosis. Functional analysis was performed to assess the prognostic value of the top 30 core genes. The CIBER-SORT algorithm was used to investigate the correlation between the immune cells and TMB subtypes. An immune prognosis model was constructed to screen out immune genes related to prognosis, and the tumor immunity assessment resource (TIMER) was then used to determine the correlation between gene expression and the abundance of tumor-infiltrating immune cell subsets in colon cancer. We observed that APC, TP53, TTN, KRAS, MUC16, SYNE1, PIK3CA have higher somatic mutations. DEGs enrichment analysis showed that they are involved in the regulation of neuroactive ligand-receptor interaction, the Cyclic adenosine monophosphate (cAMP) signaling pathway, the calcium signaling pathway, and pantothenate and Coenzyme A (CoA) biosynthesis. The difference in the abundance of various white blood cell subtypes showed that Cluster of Differentiation 8 (CD8) T cells (P=0.008), activated CD4 memory T cells (P=0.019), M1 macrophages (P=0.002), follicular helper T cells (P=0.034), activated Natural killer (NK cell) cells (P=0.017) increased remarkably, while M0 macrophages significantly reduced (P=0.025). The two immune model genes showed that secretin (SCT) was negatively correlated with survival, while Guanylate cyclase activator 2A (GUCA2A) was positively correlated.ConclusionsThis study conducted a systematically comprehensive analysis of the prediction and clinical significance of TMB in colon cancer in identification, monitoring, and prognosis of colon cancer, and providing reference information for immunotherapy.     

Tumor mutation burden determined by a 645-cancer gene panel and compared with microsatellite instability and mismatch repair genes in colorectal cancer

BackgroundTumor mutation burden (TMB) assessed by tumor-related gene panels (CRGP), microsatellite instability (MSI), and mismatch repair (MMR) has been proven to be associated with prognosis, and these factors are prognostic indicators in predicting the benefits of immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CRGPs, MSI, and MMR is associated with overall survival (OS) in patients with colorectal cancer (CRC) remains to be explored.MethodsThe prognostic threshold of the panel-TMB was explored by a panel of 645 genes (GP645) from 41 CRC patients in Jiangsu Cancer Hospital (JCH dataset). The results were further validated using 531 CRC patients from The Cancer Genome Atlas (TCGA) database.ResultsMutations of the GP645 genes were distributed on 21 chromosomes. Spearman correlation analysis showed that the panel-TMB was positively correlated with TMB measured by whole-exome sequencing (WES) (wTMB) in the TCGA dataset (R=0.75, P<0.001). Kaplan-Meier survival analysis demonstrated that higher panel-TMB in CRC patients was significantly associated with a poor OS (P=0.0062). MSI and MMR status were determined using the GP645 by next-generation sequencing (NGS). The proportions of MSI-H and dMMR accounted for less than 10% in CRC, the vast majority of MSI-H/dMMR samples also had high TMB [positive predictive value (PPV) =66.6%], and only 13.3% of samples with high TMB were classified as MSI-high/dMMR. In addition, patients with low-TMB were associated with MSS/pMMR (96.2%), and these results are consistent with earlier studies.ConclusionsGP645 was constructed to evaluate OS in Chinese CRC patients. Panel-TMB and MSI/MMR might be potential prognostic predictors of CRC patients using the GP645.     

基于TCGA数据库分析肿瘤突变负荷在肌层浸润性膀胱癌预后评估中的价值

目的：探讨肿瘤突变负荷（TMB）在肌层浸润性膀胱癌（MIBC）预后评估中的价值。方法：从TCGA数据库下载MIBC测序数据，结合临床数据分析TMB在MIBC中的临床意义，从TMB分组中识别出差异表达的免疫相关基因进行预后分析；另外采用非负矩阵分解CIBERSORT算法确定免疫细胞与TMB亚型之间的相关性。结果：纳入的375例MIBC患者样品中单核苷酸多态性（SNP）和C > T是最常见的错义突变；TP53、TTN、KMT2D、MUC16、ARID1A基因的突变率较高；与低TMB组MIBC患者相比，高TMB组的患者预后较好（P < 0.01）；以KIR2DL4、IL1RL1、SSTR5构建的COX回归模型中低风险组MIBC患者较高风险组预后更佳，曲线下面积（ROC）为0.71；与正常膀胱组织相比，高TMB组的CD8⁺ T细胞、活化的CD4⁺ T细胞、嗜酸性粒细胞表达较高，而在低TMB组中记忆B细胞及未活化的肥大细胞表达比例较高（P < 0.05）。结论：TMB较高的MIBC患者可能在免疫治疗中获得较好的预后，TMB具有预测肿瘤免疫治疗疗效的潜在应用价值；还发现了不同组分的免疫细胞在TMB分组的MIBC肿瘤微环境中存在表达差异。     

基于细胞焦亡的结肠癌预后预测模式

目的：采用生物信息学方法探索结肠癌组织中与焦亡相关的基因,并探讨其与预后的关系,为结肠癌患者提供新的治疗靶点。方法：分别从TCGA数据库、GEO数据库中下载结肠癌患者的基因表达、转录数据及临床数据。利用R软件提取出TCGA转录数据中细胞焦亡基因的表达量,并找到差异表达基因,构建差异表达基因的蛋白互作网络。采用单因素分析、聚类分析将基因进行分型,比较两种亚型之间生存差异,得到预后相关基因。然后通过Lasso回归分析、交叉验证及优化,得到基因系数（Coef系数）,构建一种结肠癌预后的预测模型。根据该预测模型计算出TCGA样本的中位风险得分,将样本分为高、低风险组。以GEO样本作为验证组,分别对TCGA、GEO样本进行生存分析（Kaplan-Meier分析）、绘制ROC曲线、绘制风险曲线、PCA和t-SNE分析。结合模型中的风险评分,分别采用单因素及多因素分析来寻找结肠癌患者的独立预后因素。对高、低风险组进行GO和KEGG分析。最后行ssGSEA分析,对每个样本进行免疫细胞及免疫相关功能打分,得到高、低风险组之间免疫细胞及免疫细胞相关功能的差异。结果：共鉴定了52个焦亡基因在结肠癌及正常结肠...     

Development and verification of a microsatellite instability-related risk signature for predicting survival and therapy effectiveness in gastric cancer

BackgroundGastric cancer (GC) is one of is one of the most common malignancy among digestive system cancers worldwide. Increasing evidence has revealed that microsatellite instability (MSI) status can affect the survival in various cancers. However, the role of MSI status in GC remains uncertain.MethodsThe RNA-seq and clinicopathological features and mutation data of GC was obtained from The Cancer Genome Atlas (TCGA). Different bioinformatic and statistical methods were combined to construct a robust MSI-related gene signature for prognosis. Gene set enrichment analysis was conducted to explore Kyoto Encyclopedia of Genes and Genomes pathways associated with the MSI-related risk signature. Moreover, Kaplan-Meier (K-M) survival and receiver operating characteristic (ROC) analyses evaluate that the MSI-related risk signature. Immune-associated miRNAs were identified using immune scores calculated by the ssGSEA. In addition, ‘pRRophetic’ R package was used to assess the chemotherapeutic response by the GDSC website.ResultsWe firstly analyzed the influence of MSI status to GC survival based on the data from the TCGA database. GC patients in the TCGA database were divided into MSI-H and MSI-L/MSS groups. We counted the survival conditions of GC patients in these two groups. In addition, we also calculated the difference of TMB between these two groups and found that MSI-H group had a relatively high survival rate. Next, we identified 99 highly mutated genes in MSI-H group and constructed a MSI-related risk signature based on 10 robust genes for predicting the overall survival (OS) of GC patients. Moreover, analyses indicated that the MSI-related risk signature can accurately predict 1-, 3- and 5-year OS of GC patients. Furthermore, enrichment analysis suggested that genes between the high- and low-risk groups mainly involved in mutation and DNA repair related pathways. Finally, we also found that the MSI-related risk signature can affect the TME immune cell infiltration in GC and can be used to predict the clinical response to immunotherapy.ConclusionsIn the present study, we develop a MSI-related risk signature for predicting the survival and therapy of GC, which may contribute to the clinical treatment of GC.     

miR-93-5p和miR-106b-5p在酒精相关性肝癌中的表达及其临床意义

目的： 探讨miR-93-5p和miR-106b-5p在酒精性肝硬化肝癌（酒精相关性肝癌）患者中的表达水平及其临床意义。方法： 选取酒精相关性肝癌患者穿刺组织蜡块10例,根据性别、年龄配对原则选取10例酒精性肝硬化患者穿刺组织蜡块,采用实时荧光定量PCR（qPCR）检测组织中的miR-93-5p和miR-106b-5p表达水平。另收集河北医科大学第四医院2014年1月1日—2016年12月31日住院治疗的酒精相关性肝癌患者资料71例,治疗前抽取患者外周血,qPCR法检测血清中miR-93-5p和miR-106b-5p的表达水平,分析miR-93-5p和miR-106b-5p表达水平与患者临床病理指标和预后的关系。结果： 酒精相关性肝癌患者癌组织中miR-93-5p和miR-106b-5p的表达水平显著高于酒精性肝硬化患者（均P<0.01）。miR-93-5p或miR-106b-5p高表达组肿瘤最大径较低表达组显著增加（P<0.01）,且临床分期较晚（P<0.01）。全组患者中,年龄<60岁组患者生存率显著优于≥60岁组患者（P=0.03）;肿瘤最大径<5 cm组患者生存率显著优于≥5 cm组患者（P=0.01）;TNM分期Ⅰ+Ⅱ期患者生存率高于Ⅲ期患者（P=0.02）;miR-93-5p或miR-106b-5p高表达组患者生存率较低表达组患者显著降低（P≤0.01）;年龄和miR-106b-5p表达水平是患者预后的独立影响因素（P值分别为0.02和0.03）。结论： miR-93-5p和miR-106b-5p有作为酒精相关性肝癌肿瘤标志物的潜力,治疗前检测其表达水平可以预测患者临床病理指标和预后。     

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

PurposeTriple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC.MethodsA kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation.ResultsThe significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively).ConclusionComprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.     

肺腺癌中预后多维转录组分子标签的构建

[目的]通过对TCGA数据库中肺腺癌数据进行挖掘,构建由编码基因(PCG)、长链非编码RNA (lncRNA)和小RNA(microRNA)组成的多维转录组分子标签.[方法]采用Cox风险回归、Kaplan-Meier法、随机生存森林、ROC分析等方法,挖掘TCGA癌症公共数据库中肺腺癌转录组二代测序数据,筛选预测效能良好的多维转录组分子标签.[结果]纳入的397例肺腺癌患者的平均年龄为65.67岁,平均生存时间为20.77个月.筛选得到由ELOVL6、RP11-446E9.2、CTD-2555C10.3、PACERR、hsa-mir-140、hsa-mir-31和hsa-mir-582构成的多维转录组分子标签对肺腺癌患者预后预测效能良好.ROC分析其预测效能显示,该分子标签AUC值为0.73,大干TNM分期的0.65(测试组:0.68 vs.0.66).该分子标签能将肺腺癌患者分成高低风险组,生存时间有显著差异(中位生存时间:25.3个月vs.85.3个月,P＜0.001;HR=2.36,95％CI:1.88～2.98,199例).在测试组Kaplan-Meier分析该多维转录分子组标签也能将患者分成高低风险组(中位生存时间:39.8个月vs.59.3个月,P＜0.05,198例).且多因素Cox回归显示该多维转录组分子标签为独立预后因子.[结论]本研究通过对TCGA数据库的挖掘,构建的多维转录组分子模型对肺腺癌患者预后有良好的指示作用,可作为潜在的肺腺癌患者预后指示标签.     

基于基因组突变数据分析肝癌预后分子标志物

目的  探讨肿瘤突变负荷（tumor mutational burden，TMB）及关键信号通路的基因变异与肝细胞癌（hepatocellular carcinoma，HCC）患者预后的相关性。 方法 从TCGA数据库及cBioPortal数据库schulze2015队列分别获取376例和243例HCC患者全外显子测序数据，从ICGC数据库获取JP队列 394例及FR 队列250例HCC患者全基因组测序数据。采用生存分析研究TMB、关键信号通路的基因变异与HCC患者预后的关系。结果 TCGA队列、JP队列、schulze2015队列和FR队列中，对数转换后的TMB与年龄均呈正相关（P<0.001）；在schulze2015队列中，对数转换后的TMB与肿瘤大小呈正相关（r=0.204，P=0.002）。在TCGA队列中，与低TMB组比较，高TMB 组HCC患者的OS（P<0.001）及DFS（P=0.088）均明显降低，高TMB组HCC患者的死亡风险是低TMB组的2.156倍（P<0.001）。JP队列和FR队列均未发现TMB与OS及DFS有统计学意义。TCGA队列、JP队列和FR队列中，细胞周期调控通路基因变异的HCC患者中位DFS和中位OS均低于无变异的患者（P<0.05），而复发风险和死亡风险均高于无变异患者（P<0.05）。结论 肿瘤突变负荷高和细胞周期调控通路的基因变异的HCC患者预后较差。     

基于生物信息学分析筛选和鉴定肝细胞癌预后相关的代谢基因

目的:寻找与肝癌发病机制和预后相关的潜在代谢基因并构建预测肝细胞癌(hepatocellular carcino-ma,HCC)患者预后模型.方法:通过GSEA数据库获得所有与代谢途径相关的基因,从TCGA数据库下载肝癌和正常组织的基因表达数据.将二者的基因相映射,分析这些代谢差异表基因(DEGs)在肝癌标本中的表达情...     

Identification of gene biomarkers and immune cell infiltration characteristics in rectal cancer

BackgroundCompared with colon cancer, the increase of morbidity is more significant for rectal cancer. The current study set out to identify novel and critical biomarkers or features that may be used as promising targets for early diagnosis and treatment monitoring of rectal cancer.MethodsMicroarray datasets of rectal cancer with a minimum sample size of 30 and RNA-sequencing datasets of rectal adenocarcinoma (READ) were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The method of robust rank aggregation was utilized to integrate differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the DEGs was structured using the STRING platform, and hub genes were identified using the Cytoscape plugin cytoHubba and an UpSet diagram. R software was employed to perform functional enrichment analysis. Receiver operating characteristic (ROC) curves based on the GEO data and Kaplan-Meier curves based on the TCGA data were drawn to assess the diagnostic and prognostic values of the hub genes. Immune cell infiltration analysis was conducted with CIBERSORT, and the diagnostic value and correlations between prognostic genes and infiltrated immune cells were analyzed by principal component analysis (PCA), ROC curves, and correlation scatter plots.ResultsA total of 137 robust DEGs were obtained by integrating datasets in GEO. Twenty-four hub genes, including CHGA, TTR, SAA1, SPP1, MMP1, TGFBI, COL1A1, and PCK1, were identified as a diagnostic gene biomarker group for rectal cancer, and SAA1, SPP1, and SI were identified as potential novel prognostic biomarkers. Functionally, the hub genes were mainly involved in the rectal cancer related interleukin (IL)-17 and proximal tubule bicarbonate reclamation pathways. Twelve sensitive infiltrated immune cells were identified, and were correlated with prognostic genes.ConclusionsThe integrated gene biomarker group combined with immune cell infiltration can effectively indicate rectal cancer.     

Association of Tumor Mutational Burden With DNA Repair Mutations and Response to Anti–PD-1/PD-L1 Therapy in Non–Small-Cell Lung Cancer

PurposeTo examine clinical predictors of tumor mutational burden (TMB), to explore the association between TMB and DNA repair mutations, and to analyze TMB as a biomarker for response to immune checkpoint blockade in non–small-cell lung cancer.Patients and MethodsTMB scores were determined retrospectively for 72 consecutive patients at our institution with next-generation sequencing comprehensive genomic profiling testing by Foundation Medicine. TMB scores were correlated with a number of clinical variables and presence of DNA repair mutations. Thirty-four patients were treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies, and survival analyses based on TMB score were performed. In addition, tissue immunohistochemical analysis was performed for a subset of patients.ResultsHistory of smoking, but not other clinical variables, including prior treatment lines, stage of disease, and number of metastatic sites, predicted higher TMB score. Higher TMB score was significantly associated with greater number of DNA repair mutations. In the subset of patients treated with immune checkpoint blockade, higher TMB score significantly predicted overall survival, but not progression-free survival (hazard ratio = 0.10, P = .003; hazard ratio 1.1, P = .84, respectively). In a small subset of patients, PD-1/PD-L1 staining did not independently predict progression-free survival or overall survival.ConclusionTissue TMB was significantly associated with smoking history and number of DNA repair mutations. TMB is a promising biomarker for response to anti–PD-1/PD-L1 therapy, with higher TMB score predicting longer overall survival.     

非小细胞肺癌关键基因的生物信息学分析

目的:通过生物信息学方法挖掘非小细胞肺癌(NSCLC)基因表达谱芯片数据,筛选并验证与NSCLC发生和预后相关的关键基因。方法:从Gene Expression Omnibus(GEO)数据库中下载芯片数据(GSE101929和GSE27262)。采用GEO2R在线工具筛选癌组织和癌旁组织中的差异表达基因(DEGs);采用DAVID在线工具对差异表达基因进行GO和KEGG信号通路分析并用Cytoscape和FunRich软件进行可视化;采用GEPIA在线工具对差异表达基因进行验证和预后分析。结果:共筛选出1816个差异表达基因,其中上调基因数651个,下调基因数1165个。上调基因主要富集在“基质金属肽酶活性”,下调基因主要富集在“受体活性”等分子功能。KEGG信号通路分析显示上调基因主要富集在“有丝分裂前中期”等信号通路,而下调基因主要富集在“上皮-间质转化”信号通路。蛋白-蛋白交互作用(PPI)分析显示,上调基因中的前五位为TOP2A、CDK1、CCNB1、CCNA2和KIF11,而下调基因中的前五位为IL6、FGF2、LRRK2、EDN1和IL1B。总生存率分析显示,KIF11低表达与NSCLC预后呈负相关。结论:本研究鉴定出了与NSCLC相关的关键基因,有望作为NSCLC患者潜在治疗靶点或预后判断相关的生物标志。     

The functions and prognostic values of chemokine and chemokine receptors in gastric cancer

Chemokine and chemokine receptors (CCRs) play a significant role in tumor infiltration of immune cells, tumor angiogenesis and distant metastasis. In this study, we explored the importance of CCRs in gastric cancer (GC) by analyzing the datasets from TCGA database. First, we analyzed the characteristics of the CCRs mutations. Then, we screened the differentially expressed CCRs and performed GO functional annotation and KEGG pathway analyses to explore their potential biological functions. Using multivariate Cox regression analyses, we constructed a prediction model based on four-CCRs (CCL15, CCL21, CCR3 and ACKR3) signature, and we found that the risk score of the model was an independent prognostic factor of GC. Next, a nomogram was constructed to assess the prognosis of GC patients. GSEA indicated that the high-risk group was significantly enriched in immune response and immune system process. Moreover, GSVA was employed to investigate the up- and down-regulated signaling pathways in the high- and low-risk groups. The correlation between risk score and immune-cell infiltration indicated that the four-CCRs signature might play a pivotal role in GC immune microenvironment. In conclusion, we revealed the potential molecular mechanisms of CCRs in GC and constructed a prediction model which might guide personalized treatment and prognosis for GC patients.     

TTN突变相关基因特征对肝细胞肝癌预后的预测价值

目的:寻找新的有效生物标志物用于肝细胞肝癌(hepatocellular carcinoma,HCC)的早期诊断和预后预测。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载HCC样本的转录组和临床数据,利用TCGA队列的mRNA丰度数据和TTN突变信息,根据野生型TTN和突变型TTN HCC患者之间的基因表达差异,表征特定的TTN突变相关特征。生存分析筛选与HCC患者预后相关的基因,单因素Cox回归构建预后风险模型。通过GO注释、途径富集分析、京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)确定与HCC患者预后相关的差异表达基因(differentially expressed genes,DEGs)的功能。结果:通过单变量Cox回归和Kaplan-Meier生存分析确定的5个基因,腹前同源盒1(ventral anterior homeobox 1,VAX1)、基质金属蛋白酶3(matrix metalloproteinase 3,MMP3)、CXC型趋化因子5（CXC-type chemokine 5,CXCL5)、转酮醇酶样蛋白1(transketolase-like protein 1,TKTL1)和电压门控钾通道Kv1.3(voltage-gated potassium channel Kv1.3,KCNA3)构成了HCC患者总生存(overall survival,OS)预后基因特征。结论:5个TTN突变相关基因,包括VAX1、MMP3、CXCL5、TKTL1和KCNA3,可作为HCC患者生存和预后的潜在生物标志物和治疗靶点。     

Evaluation of 30 DNA damage response and 6 mismatch repair gene mutations as biomarkers for immunotherapy outcomes across multiple solid tumor types

Objective:DNA damage response (DDR) genes have low mutation rates, which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor (ICI) treatment. Thus, a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database. A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center (FUSCC). A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis. A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute (DFCI) cohort were obtained from a published dataset. The Cancer Genome Atlas (TCGA) level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study. Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI, and most of them predicted the therapeutic efficacy of ICI, in a manner dependent on TMB, except for 4 combined DDR gene mutations, which were associated with the therapeutic efficacy of ICI independently of the TMB. Single MMR/DDR genes showed low mutation rates; however, the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high, reaching 10%–30% in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.     

肺腺癌中免疫治疗相关氧化应激基因表达的临床意义及其与免疫细胞浸润和药物敏感性的关系

目的：探究肺腺癌中与免疫治疗相关氧化应激基因（IROSG）及其与肿瘤组织免疫浸润和患者预后的关系。方法：从TCGA数据库和GEO数据库下载肺腺癌患者IROSG表达数据及相关临床信息。对非小细胞肺癌免疫治疗队列进行差异基因表达分析以获取免疫治疗相关基因,然后与从GeneCards数据库筛选的氧化应激相关基因取交集得到IROSG。基于得到的IROSG对肺腺癌患者进行分型,对亚型的差异表达基因进行单因素COX、LASSO和多因素COX回归分析以构建预后模型。使用模型公式计算每个患者的风险评分,并将患者划分为高、低风险组。从多个层面验证模型的预测效能,并进行肿瘤微环境（TME）分析、免疫治疗反应预测和药物敏感性分析。结果：通过数据库分析获取82个IROSG,IROSG高表达的肺腺癌患者预后较好（P<0.05）。基于IROSG表达水平分型和风险评分构建的肺腺癌患者预后模型预测能力好,基于风险评分和病例特征等预后因子构建的列线图和校正曲线能较好地预测肺腺癌患者的总生存率。低风险组主要富集于同种异体移植物排斥和自身免疫性疾病等通路,而高风险组主要富集在细胞周期和DNA复制等通路上,且低风险组肺...     

基于TCGA数据库探究肾透明细胞癌关键基因的表达及预后作用

目的:探究肾透明细胞癌中关键基因的表达及预后作用,寻找潜在治疗靶点。方法:从TCGA数据库下载肾透明细胞癌mRNA的表达数据,通过Rstudio软件分析肿瘤与正常组织间差异表达基因,对差异表达基因进行富集分析、蛋白-蛋白相互作用网络构建,并分析出关键基因,最后对关键基因进行预后分析。结果:得到1 855个差异表达基因,其中有1 207个是上调的,648个是下调的,富集分析发现差异基因主要与信号转导、物质代谢、免疫反应等信号通路相关。筛选出10个关键基因中有6个存在预后价值。结论:筛选出的差异基因及信号通路可以帮助我们探索肾透明细胞癌发病的分子机制,同时为靶向治疗的研究提供潜在的理论依据。