转录组分析鉴定腰椎椎间盘退行性变中潜在免疫相关生物标志物

目的 通过转录组分析鉴定腰椎椎间盘退行性变（IDD）中潜在的免疫相关生物标志物，寻找IDD免疫相关的关键靶点。方法 从基因表达汇编数据库（GEO）的GSE67567数据集中获得基因表达谱，并筛选差异表达mRNA、长链非编码RNA（lncRNA）和微RNA（miRNA）。使用加权基因共表达网络分析（WGCNA）和基因集富集分析（GSEA）筛选免疫相关模块，并使用Cytoscape构建lncRNA-miRNA-mRNA竞争性内源RNA（ceRNA）网络，通过免疫浸润分析确定相关的免疫细胞，使用Pearson相关分析筛选免疫相关的关键靶点。通过GSEA筛选关键的生物过程和途径。使用GEO的GSE124272数据集验证关键靶基因的表达。结果 WGCNA结果表明，蓝绿色模块与免疫力有关。免疫浸润分析显示，CD4幼稚T细胞可能是关键的免疫细胞。Pearson相关分析表明，4个mRNA（UHMK1、ZFP36L2、ZCCHC3、ZBTB20）和1个lncRNA（LINC00641）可能是IDD免疫相关的关键靶点，建立了一个免疫调节相关的ceRNA网络。GSEA结果显示，LINC00641可能通过TGF-β信号通路调节IDD。验证结果表明，这些关键基因在GSE124272数据集中存在差异表达。结论 mRNA（UHMK1、ZFP36L2、ZCCHC3、ZBTB20）和lncRNA（LINC00641）是IDD免疫相关的关键靶点。     

基于不同数据库来源数据的胃癌长链非编码RNA预后预测模型构建

背景与目的：长链非编码RNA（lncRNA）对于胃癌患者的预后判断有着非常显著的影响。本研究旨在通过生物信息学的方法,构建并验证能够准确评估胃癌患者预后的lncRNA预后预测模型。 方法：通过癌症基因组图谱（TCGA）数据库、基因型-组织表达数据库（GTEx）获取数据作为用于构建预后模型（建模组）,通过基因表达汇编数据库（GEO）获取数据用于验证（验证组）。采用R软件中的edgeR包筛选差异表达lncRNA;通过单因素和多因素Cox回归来构建预后模型并计算风险值;按照风险值的大小将患者分为高、低风险组,分析风险值与临床病理参数及预后的关系。用验证组样本对建模组的结果进行验证。 结果：共筛选出288个差异表达lncRNA,其中28个与胃癌预后有关（均P<0.05）。10种lncRNA生物标记物（MEG3、DNAJC9-AS1、ACTA2-AS1、C15orf54、LINC01210、OVAAL、POU6F2-AS2、ERICH3-AS1、LINC00326及LINC01526）被鉴定并用于构建预后模型。高风险组的总体生存率以及无病生存率均低于低风险组（均P<0.01）,ROC曲线证实该预测模型有一定的准确性（AUC=0.700）。单因素及多因素Cox回归分析显示风险值为独立的预后因子（均P<0.001）。风险值与胃癌T分期（P=0.031）、肿瘤分化程度（P=0.044）存在明显关系。在独立的验证组中,高风险组的总体生存率以及无病生存率同样明显低于低风险组,且示风险值依旧为独立的预后因子（均P<0.05）。 结论：所构建的10-lncRNA模型对于胃癌患者的预后生存判断有一定的价值,且筛选出的差异表达lncRNA为胃癌分子机制的深入研究提供了依据。     

乳腺癌中垂体瘤转化基因1对免疫浸润的影响及其预后价值

背景与目的 垂体瘤转化基因1（PTTG1）是一种癌基因,在多种肿瘤中高表达,可作为癌症侵袭转移的生物标志物。然而,PTTG1在乳腺癌中的表达水平及其与患者预后的关系并不清楚。本研究旨在研究乳腺癌中PTTG1的表达与患者预后的关系及其对免疫细胞浸润的影响,并初步探讨PTTG1在乳腺癌发生发展中的可能作用机制。方法 利用Oncomine 4.5数据库和Kaplan-Meier Plotter数据库分析乳腺癌组织中PTTG1的表达情况及其预测患者预后的价值。Coexpedia筛选出PTTG1的共表达基因,并通过GO数据库和KEGG数据库分析其共表达基因富集的通路情况。TIMER数据库用于分析乳腺癌中PTTG1基因表达水平与免疫细胞浸润的关系。采用multiMiR的R语言包预测与PTTG1及其共表达基因相互作用的microRNA,并使用Cytoscape进行网络可视化。结果 PTTG1在乳腺癌组织中表达明显升高,且高表达PTTG1患者的预后明显差于低表达PTTG1的患者（P<0.001）。乳腺癌中PTTG1基因及其共表达基因集GO功能主要富集在核分裂、细胞器分离及染色体分离上,KEGG通路富集则集中在细胞周期、减数分裂、人类T淋巴细胞白血病病毒Ⅰ型（HTLV-1）感染和p53信号转导通路上。PTTG1的表达水平与CD4+ Th1细胞（r=0.490,P=3.52e-61）、CD4+ Th2细胞（r=0.765,P=3.7e-192）、巨噬细胞（r=0.308,P=2.8e-23）、B细胞（r=0.228,P=3.69e-13）和中性粒细胞（r=0.121,P=1.27e-04）的浸润水平呈明显正相关,与CD8+T细胞浸润水平呈明显负相关（r=-0.198,P=3.16e-10）。用multiMiR R语言数据包分析发现共有17个共同靶向PTTG1及其共表达基因的microRNA。结论 PTTG1在乳腺癌组织高表达并与患者的不良预后相关,PTTG1在乳腺癌中的表达水平与免疫浸润密切相关。PTTG1高表达可能通过调控细胞周期和p53信号通路而使得肿瘤增殖和侵袭能力增强,进而导致乳腺癌的不良预后。PTTG1可能在乳腺癌中发挥癌基因的作用,提示PTTG1可以作为乳腺癌潜在的诊断和预后标记物。     

突变型p53与Nampt在胃癌组织中的表达及其与预后的关系

目的：探讨突变型p53（mutp53）和尼克酰胺磷酸核糖转移酶（Nampt）在胃癌组织中的表达及其对患者预后的影响。方法：用免疫组化法检测68例胃癌患者胃癌组织及癌旁正常胃黏膜组织中p53（免疫组化检测到的p53主要为mutp53）与Nampt的表达,分析mutp53与Nampt表达与患者临床病理因素及预后的关系。 结果：胃癌组织中mutp53与Nampt的阳性表达率均明显高于癌旁正常胃黏膜组织（均P<0.05）;mutp53的高表达与肿瘤大小、浸润深度、淋巴结转移及TNM分期有关,而Nampt的高表达与肿瘤浸润深度、淋巴结转移及TNM分期有关（均P<0.05）。胃癌组织中,p53表达与Nampt表达呈明显正相关（r=0.982,P<0.05）。p53阳性表达患者的中位生存期明显短于阴性表达患者,且在p53阳性表达患者中,Nampt同时阳性患者的中位生存期明显短于Nampt阴性患者（均P<0.05）。结论：mutp53与Nampt的表达均与胃癌的恶性生物学行为相关,且两者存在一定的关联性,同时高表达患者预后差。

     

体质量指数变化与老年胃癌患者营养状态和预后的关系

目的：探讨体质量指数（BMI）变化与老年胃癌患者营养状态和预后的关系。 方法： 纳入老年（≥65岁）胃癌患者116例，计算患者入院前1年内BMI变化量，根据血清白蛋白值和淋巴细胞总数计算预后营养指数（PNI），采用Pearson相关分析BMI变化量与PNI的相关性。通过ROC曲线、生存分析和COX风险回归模型评价BMI变化量与患者预后的关系。 结果：116例老年胃癌患者的BMI变化值（降低）为（2.67±2.11）kg/m2，PNI为44.18±9.31，两者呈负相关（r=-0.87，P=0.003）；BMI变化量预测患者死亡的敏感性为72.73%，特异性为73.34%，分界值为3.36 kg/m2（P<0.001）；按该值将患者分为高BMI变化量组（BMI降低值≥3.36 kg/m2）和低BMI变化量组（BMI降低值<3.36 kg/m2）比较，结果显示，两组患者在PNI、分化程度、肿瘤最大径、浸润深度、淋巴转移、TNM分期和手术根治度上差异有统计学意义（均P<0.05）；高BMI变化量组生存率明显低于低BMI变化量组（P<0.05）；BMI变化量是老年胃癌患者预后的独立影响因素（HR=1.72，95% CI=1.31~2.26，P=0.002）。 结论：BMI变化能较好地反映老年胃癌患者的炎症营养状态，BMI显著降低者预后不良。

     

肿瘤最大径最佳截点与结直肠癌临床特点及预后的关系

目的：分析结直肠癌肿瘤最大径最佳截点及其与患者临床病理特点及预后的关系。方法：选择2006年1月—2012年7月行结直肠癌根治术与术后行规范化辅助治疗的结直肠癌患者 119例的临床资料。采用Kaplan-Meier生存分析方法,筛选结直肠癌肿瘤最大径的最佳截点值;分析肿瘤最大径与结直肠癌患者临床病理因素的关系,并分析结直肠癌患者预后影响因素。结果：以最大径4 cm为截点,两侧患者生存率差异最明显（65.5% vs. 51.1%,χ2=9.922,P=0.002）,故确定结直肠癌肿瘤最大径最佳截点值为4 cm。肿瘤最大径<4 cm患者与≥4 cm患者在肿瘤T分期、淋巴结检出总数、血清CEA方面差异有统计学意义（均P<0.05）。单因素分析显示,肿瘤最大径、T分期、M分期、血清CEA水平、是否输血与结直肠癌预后有关（均P<0.05）;多因素分析表明,肿瘤最大径、T分期、是否输血是结直肠癌预后的独立影响因素（均P<0.05）;按肿瘤最大径分层分析,T分期是≥4 cm患者预后的独立影响因素（HR=2.244,95% CI=1.079~4.665,P=0.030）,但以上因素对肿瘤最大径<4 cm患者预后影响不明显（均P>0.05）。结论：肿瘤最大径可作为影响结直肠癌预后的独立影响因素,其最佳截点值为4 cm,参照该截点值,有助于对患者临床特点及预后作出判断。

     

胃癌抗氧化相关lncRNAs预后风险评分模型的构建及生信分析

目的 ：探讨抗氧化相关长链非编码RNAs(lncRNAs)预后风险评分模型对胃癌患者预后的判断价值以及与免疫微环境的关系。方法：通过TCGA数据库下载胃癌转录组数据和临床信息。通过lnc RNAs和抗氧化基因的共表达分析得到抗氧化相关lncRNAs。使用单因素cox回归分析和lasso回归分析筛选并构建风险评分。采用Log-Rank检验比较两组间的生存差异。应用受试者工作特征（ROC）曲线评估预后风险模型对患者预后判断的特异性及敏感度。结合风险评分和临床参数构建列线图。TIMER2.0在线评估每个样本的免疫细胞浸润情况。TIDE网站在线分析每个样本对免疫治疗敏感性。结果：通过单因素cox回归分析和lasso回归分析构建了一个包括12个lncRNAs的风险评分。风险评分是患者预后的独立影响因素[HR=5.406(3.131～9.335),P<0.001]。风险评分与多种抑制性免疫细胞浸润呈正相关（M2型巨噬细胞、肿瘤相关成纤维细胞）。同时发现,高风险组存多种免疫检查点基因的异常表达,TIDE评分更高,提示高风险组对免疫治疗更敏感。结论：基于抗氧化相关lncRNAs风险评分和临床参数...     

乳腺癌患者外周血CD4+CD25+Foxp3+调节性T细胞水平的检测及意义

目的：探讨乳腺癌患者外周血CD4+CD25+Foxp3+调节性T细胞（Treg）水平检测的意义。 方法：流式细胞术检测74例乳腺癌患者与30例健康对照者外周血CD4+CD25+Foxp3+Treg占CD4+T细胞百分比,分析CD4+CD25+Foxp3+Treg细胞水平与乳腺癌患者临床病理特征及相关免疫组化指标的关系。 结果：乳腺癌患者外周血CD4+CD25+Foxp3+Treg占CD4+T细胞的百分比高于健康对照者[（9.15± 2.24）% vs.（2.29±1.36）%],差异有统计学意义（P<0.05）。统计分析显示,乳腺癌患者外周血CD4+CD25+Foxp3+Treg细胞水平与肿瘤组织学分级、淋巴结转移、pTNM分期以及HER-2、pS2、nm23的表达有关（均P<0.05）,而与肿瘤大小、病理类型以及雌激素受体（ER）、孕激素受体（PR）、p53、Ki-67表达无关（均P>0.05）。进一步相关性分析显示,CD4+CD25+Foxp3+Treg细胞水平与肿瘤组织学分级、淋巴结转移数、pTNM分期、HER-2的表达呈正相关（r=0.583,r=0.333,r=0.919,r=0.604,均P<0.05）而与pS2、nm23表达呈负相关（r=-0.229,r=-0.401,均P<0.05）。 结论：乳腺癌患者外周血CD4+CD25+Foxp3+Treg细胞水平升高,并与与乳腺癌的进展、转移密切相关,对其检测可能有助于患者预后及治疗效果的评估。

     

β-微管蛋白的表达对胃癌根治术后辅助化疗的影响及其与预后的关系

目的：探讨胃癌患者胃癌组织中β-微管蛋白表达水平对胃癌根治术后紫杉醇化疗效果的影响。方法：选择接受胃癌根治术并术后进行紫杉醇辅助化疗的332例胃癌患者的组织样本,采用 RT-PCR法检测β-微管蛋白的mRNA表达水平,分析患者临床特征与β-微管蛋白mRNA表达的关系;Kaplan-Meier法比较β-微管蛋白高、低表达组生存时间的差异。结果：β-微管蛋白的mRNA表达水平与患者年龄、性别、肿瘤部位和肿瘤大小均无明显关系（均P>0.05）,而与分化程度、TNM分期、淋巴结转移和远处转移有关（均P<0.05）;β-微管蛋白的mRNA高表达组患者的术后生存时间比低表达组患者术后生存时间短,差异有统计学意义（P<0.05）。结论：胃癌组织中的β-微管蛋白表达水平与胃癌根治术及术后紫杉醇辅助化疗患者的远期生存率有密切关系,可作为患者预后的判断指标。

     

pre-miR-146a基因rs2910164位点单核苷酸多态性与胆管癌的关系

目的：探讨pre-miR-146a基因表达及其rs2910164位点多态性与胆管癌的关系。 方法：分别用基因直接测序与定量PCR方法检测70例胆管癌患者的胆管癌组织（胆管癌组）及 39例胆管非肿瘤性疾病患者的胆管组织（对照组）中pre-miR-146a基因rs2910164位点单核苷酸多态性与pre-miR-146a表达,分析不同基因型与pre-miR-146a表达量、胆管癌临床病理及其预后的关系。 结果：胆管癌组的pre-miR-146a基因型分布与对照组有明显差异,前者表现为GG和GC基因型比例明显高于CC基因型,且G等位基因频率明显高于C等位基因（均P<0.05）;对照组GG和GC基因型人群的pre-miR-146a表达量较CC基因型低,但差异无统计学意义（P>0.05）,胆管癌组织pre-miR-146a表达量明显低于对照组胆管组织（P<0.05）;Logistic多元回归分析显示GG和GC基因型可能是胆管癌的危险因素（P=0.052）,分层分析显示GG和GC基因型与胆管癌患者的临床分期和淋巴结转移有关（均P<0.05）;生存分析显示GG和GC基因型胆管癌患者的生存率低于CC基因型胆管癌患者,但差异无统计学意义（P=0.178）。 结论：pre-miR-146a基因rs2910164位点G等位基因频率升高可能是导致pre-miR-146a基因表达降低以及胆管癌发生发展的危险因素。

     

The expression of long non-coding RNA LINC01279 in gastric adenocarcinoma and its clinical significance

ObjectiveTo investigate the expression of long non-coding RNA LINC01279 in gastric cancer and its relationship with the clinicopathological features and prognosis of gastric cancer patients.MethodsSerum, gastric cancer and adjacent tissue samples from 90-patients with gastric-cancer treated by surgery and serum samples from 90-healthy adults were collected. The expression level of LINC01279 was analyzed by RT-PCR. The clinical baseline data of gastric cancer patients were obtained. Correlation between the expression level of LINC01279 and the clinicopathological characteristics of gastric cancer patients was assessed.ResultsLINC01279 was highly expressed in gastric cancer tissues and serum of gastric cancer patients (P < 0.05). The expression level of lncRNA 01279 was closely related to vascular invasion, nerve invasion, T-stage, lymph node metastasis, and advanced clinical-stage of gastric cancer (P < 0.05). The expression level was not correlated with gender, age, tumor size, location, and differentiation. There was a significant negative correlation between the expression of LINC01279 and the overall survival of gastric-cancer patients (P < 0.05).ConclusionLINC01279 is highly expressed in gastric-cancer tissues and serum, which is closely related to tumor-invasion. Serum LINC01279 is a better prognostic indicator of invasive cancer than current tumor markers.     

长链非编码RNA 909靶向调控miR-194-5p/DACH1轴对胰腺癌细胞增殖、迁移和侵袭的影响

背景与目的:长链非编码RNA 909(LINC00909)是一个新发现的长度约为2 kb的长链非编码RNA(lncRNA),在胶质瘤和白血病中被报道发挥癌基因的作用.然而LINC00909在胰腺癌中的作用鲜有报道.本研究旨探讨LINC00909在胰腺癌中的表达及其对患者预后的影响,以及LINC00909与其调控网络对胰...     

肝细胞癌免疫相关lncRNA预后风险模型的建立与评估

背景与目的:肝细胞癌(HCC)目前是全球肿瘤死亡的主要原因之一,越来越多的证据表明,长非编码RNA (lncRNA)可以作为肿瘤预后的生物标志物.然而,lncRNA与HCC生存预后的关系仍未阐明.本研究筛选HCC预后免疫相关lncRNA,并构建预后风险模型.方法:从癌症基因组图谱(TCGA)中下载HCC转录组数据和临床...     

C3, C3AR1, HLA-DRA,and HLA-E as potential prognostic biomarkers for renal clear cell carcinoma

BackgroundPrognostic biomarkers play a vital role in the early detection of the cancer and assessment of prognosis. With advances in technology, a large number of biomarkers of kidney renal clear cell carcinoma (KIRC) have been discovered, but their prognostic value has not been fully investigated, and thus have not been widely used in clinical practice. We aimed to identify the reliable markers associated with the prognosis of KIRC patients.MethodsWe obtained 72 normal samples and 539 tumor samples from The Cancer Genome Atlas (TCGA), and 23 normal samples and 32 tumor samples from the Gene Expression Omnibus (GEO). Overlapping differentially expressed genes (ODEGs) were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, followed by construction of a protein-protein interaction (PPI) network to screen hub genes. Kaplan-Meier analysis, univariate Cox analysis, multivariate Cox analysis, Wilcoxon signed-rank test, Kruskal-Wallis test, and gene set enrichment analysis (GSEA) were performed to verify the prognostic value and function of the markers we selected. The relationships among gene expression level, tumor immune cell infiltration, and immune-checkpoints were also analyzed.ResultsA total of 910 genes were screened out, and C3, C3AR1, HLA-DRA, and HLA-E were identified as potential tumor markers. The expression of each gene was closely associated with tumor immune cell infiltration, survival rate, and the patients’ clinical characteristics (P<0.05). C3AR1, HLA-DRA, and HLA-E were also verified as independent prognostic factors of KIRC (P<0.05), and all these potential biomarkers had a close correlation with immune checkpoints.ConclusionsC3, C3AR1, HLA-DRA, and HLA-E could be reliable biomarkers of KIRC and may have a significant contribution to make in immunotherapy, thus playing an important role in the improvement of prognosis.     

Identification of new biomarkers in immune microenvironment of testicular germ cell tumour

To seek novel prognostic biomarkers for testicular germ cell tumour (TGCT) and investigate the tumour immune microenvironment, we identified critical differentially expressed genes (DEGs) by overlapping GSE1818 dataset from Gene Expression Omnibus (GEO). Protein–protein interaction (PPI) network was used to investigate key modules and hub genes. Functional enrichment analysis was performed to investigate the underlying molecular functions of the DEGs in TGCT development and progression. The following survival analysis based on The Cancer Genome Atlas (TCGA) TGCT dataset indicated that AKAP4, SPA17 and TNP1 are correlated with TGCT prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction verified the down-regulation of the 3 hub genes in TGCT. Gene set enrichment analysis was conducted to further explore the role of the 3 hub genes in TGCT respectively. In addition, TGCT samples had high infiltration of CD8+ T cells, M0 and M1 macrophage cells, and resting myeloid dendritic cells in immune microenvironment. We also constructed the microRNA-gene regulatory networks to identify the key upstream microRNAs in TGCT. In conclusion, our findings indicated that AKAP4, SPA17 and TNP1 are promising biomarkers of TGCT. AKAP4 and TNP1 might regulate immune cells infiltration in immune microenvironment.     

Pretreatment serum C-reactive protein is a significant prognostic factor in patients with soft tissue metastases

BackgroundSoft tissue metastasis is rarer than bone metastasis. Patients with soft tissue metastasis generally have a dismal prognosis. The treatment for metastatic lesions is sometimes difficult, because the prognostic factors of patients with soft tissue metastasis remain unelucidated. Therefore, this study aimed to identify these prognostic factors.MethodsThirty-one patients with soft tissue metastasis were included in the study. We evaluated associations of overall survival with clinical parameters and inflammatory markers using Kaplan–Meier curves and Cox proportional hazards models.ResultsTwelve patients received surgery for soft tissue metastasis, while radiation therapy was performed in six cases. The median overall survival after the detection of soft tissue metastasis was 11 months. Univariate analysis revealed that detection of soft tissue metastasis after the multidisciplinary treatment (P = 0.01); solitary metastasis (P = 0.0003); and pretreatment C-reactive protein (CRP) level < 0.4 mg/dL (P < 0.0001), white blood cell count < 8500 × 10³/μL (P = 0.0003), and neutrophil-to-lymphocyte ratio < 5 (P = 0.02) were significant good prognostic factors. Multivariate analysis revealed that a CRP value < 0.4 mg/dL (P = 0.07) and solitary metastasis (P = 0.09) were possible significant predictors of survival. Furthermore, in case of CRP levels <0.4 mg/dL and metastatic tumor resection, patients had a good prognosis; however, when the CRP levels increased to 0.4 mg/dL and above, patients had a poor prognosis, irrespective of tumor resection.ConclusionsCRP is potentially useful for determining the indication of radical metastasectomy in soft tissue metastasis.     

Prognostic value of node skip metastasis on esophageal cancer: A systematic review and meta-analysis

The association between NSM and prognosis of esophageal cancer remains controversial, though several studies have been conducted drawing their own conclusion. Therefore, we firstly carried out this meta-analysis aiming to explore the association. We performed a comprehensive literature search online, including PubMed, Embase and Web of Science. We selected deaths at 5 years and hazard ratio (HR) with 95% (CI) to perform the meta-analysis with Review Manager 5.3, predicting value of clinic-pathological features in NSM also been analyzed. A total of 7 studies were finally enrolled in this study. NSM, defined by either JSED criterion or anatomical compartment criterion, neither showed significant prognostic value on OS of esophageal cancer (P = 0.64), (P = 0.24). Subgroup analysis of JSED criterion, NSM was not a prognostic factor in solitary node metastasis patients (P = 0.39), whereas NSM demonstrated a poor prognostic factor (P = 0.01) for ESCC. Subgroup analysis according to anatomical criterion, NSM was a favorable factor for OS in middle thoracic ESCC (P = 0.003). Pathological N1 status was found to be a risk factor for NSM (P < 0.00001) according to JSED criterion and middle thoracic ESCC was identified as a predictor for NSM (P = 0.0003) according to anatomical compartment criterion. According to JSED criterion, NSM demonstrated poor prognosis on ESCC and N1 status was a risk factor for NSM. Concerning the anatomical compartment criterion, a favorable prognosis of NSM was found in middle thoracic ESCC and NSM was prone to occur in middle thoracic ESCC. CRD42021219333.