基于铁死亡相关基因的口腔鳞状细胞癌的生物信息学分析

目的:探究铁死亡相关基因在口腔鳞状细胞癌(OSCC)发生发展中的作用,初步确定潜在生物标志物.方法:从癌症基因组图谱数据库(TCGA)中下载头颈部鳞状细胞癌相关临床数据并筛选得到OSCC相关数据.利用R软件筛选差异表达的铁死亡相关基因并对差异表达基因进行GO和KEGG富集分析.利用STRING数据库构建蛋白质相互作用网络并利用R软件筛选关键基因.对关键基因进行Kaplan-Meier生存曲线绘制和Cox回归分析.结果:共筛选出44个铁死亡相关差异表达基因,进一步分析发现9个关键基因,其中IFNG和EGFR在OSCC组织中的表达水平与生存率显著相关(P<0.05).结论:铁死亡相关基因IFNG和EGFR可作为口腔鳞状细胞癌患者预后潜在的标志物.     

mTOR调控口腔鳞状细胞癌增殖转移的机制研究

目的：研究Toll样受体4（TOLL-like receptor 4,TLR4）分子高表达与口腔鳞状细胞癌预后的关系,探讨哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）通过TLR4信号通路间接调控口腔鳞状细胞癌增殖转移的潜在机制。方法：采用免疫组织化学法检测50例口腔鳞状细胞癌患者病理切片中TLR4的表达;使用mTOR抑制剂(雷帕霉素)作用于口腔鳞状细胞癌细胞系CAL27后,再用LPS激活TLR4信号通路,通过MTT法检测CAL27细胞的增殖能力,Transwell法检测CAL27细胞的迁移能力, Western 免疫印迹检测其对肿瘤细胞中NF-κB 及MAPK信号通路的影响。采用SPSS 16.0软件包对数据进行统计学分析。结果：TLR4分子高表达与口腔鳞状细胞癌预后差显著相关（P<0.05）;雷帕霉素能够显著抑制TLR4激活后的CAL27细胞的增殖和迁移能力（P<0.01）,显著抑制TLR4下游的NF-κB 及MAPK信号通路（P<0.01）。结论： mTOR通过TLR4信号通路调控口腔鳞状细胞癌的增殖与转移,有望成为治疗口腔鳞状细胞癌的新靶点。     

口腔癌和癌前病变细胞中氧化应激相关基因差异表达

目的 筛选口腔鳞状细胞癌和癌前病变细胞中与氧化应激相关的差异表达基因,探讨氧化应激损伤与口腔癌发生的相关性及其作用机理.方法 采用核酸微阵列技术,对口腔鳞状细胞癌细胞株Tca8113、KB及口腔癌前病变细胞株DOK细胞的基因表达谱进行比较研究,检测、筛选口腔鳞状细胞癌中与氧化应激相关的差异表达基因.结果 与氧化应激相关的差异表达基因有28条.与氧化应激关系较密切的差异表达基因有9条,如过氧化物酶、超氧化物歧化酶、谷胱甘肽合成酶、谷胱甘肽S-转移酶、硫氧还原酶及硒蛋白等.另外,细胞角蛋白17、细胞角蛋白10及细胞角蛋白7在Tea8113和KB细胞中表达明显增高.结论 氧化应激损伤可能通过某种信号通路引起细胞角蛋白发生变化,从而导致口腔鳞状细胞癌的发生.氧化应激损伤可能与口腔鳞状细胞癌的发生密切相关.     

口腔鳞状细胞癌转移相关基因实时定量PCR的验证

目的 对应用基因表达谱芯片从高低转移潜能的口腔鳞癌细胞系中筛选出的差异表达基因,进行基因转录水平的定量验证,筛选转移相关的基因.方法 选择基因表达谱芯片检测发现的、在高低转移潜能的口腔鳞癌细胞系中的差异表达基因,应用实时定量PCR定量检测方法,在口腔鳞癌低转移细胞系Tca8113及其配对的高转移亚细胞系Tb细胞中,进行基因转录水平的检测.将两种检测结果进行对比分析,筛选出可能与口腔鳞癌转移有关的基因或信号转导通路.结果 选择9个基因进行研究.其中有6个基因在高转移的Tb细胞中高表达,1个基因表达下调,2个基因在Tb和Tca8113细胞中表达无明显差异.实时定量PCR检测结果与基因芯片结果的符合率为66.7%.NF-κB信号转导通路中的主要基因A20、IκBα、TANK和p65在Tb细胞中表达明显上调.结论 NF-κB信号通路和其它一些基因,如IER3、CD44和GPMNB可能在口腔鳞状细胞癌侵袭和转移过程中发挥重要作用,这些基因和信号通路为深入研究口腔鳞癌转移的分子机理和治疗靶点奠定了基础.     

DZIP1通过影响Wnt/β-catenin信号通路促进口腔鳞状细胞癌增殖、迁移和侵袭

目的　探究DZIP1通过Wnt/β-catenin信号通路对口腔鳞状细胞癌增殖、迁移和侵袭的影响。方法　实时荧光定量PCR和Western blot检测DZIP1和Wnt/β-catenin信号通路相关基因mRNA表达和蛋白表达,CCK-8检测细胞活力,克隆形成实验检测口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）细胞增殖能力,Transwell实验检测细胞迁移和侵袭能力。结果　与人口腔角质形成细胞相比,人OSCC细胞系TSCCA,Tca8113和SCC25中DZIP1的mRNA表达和蛋白表达均显著升高;与阴性对照组（negative control,NC）相比,敲低DZIP1显著降低SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05）,显著降低细胞活力（P<0.05）,显著抑制细胞增殖（P<0.05）,显著降低细胞迁移和侵袭能力（P<0.05）,LiCl显著升高SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05）,显著升高细胞活力（P<0.05）,显著促进细胞增殖（P<0.05）,显著升高细胞迁移和侵袭能力（P<0.05）;与si-DZIP1组相比,si-DZIP1+LiCl显著升高SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05）,显著升高细胞活力（P<0.05）,显著促进细胞增殖（P<0.05）,显著升高细胞迁移和侵袭能力（P<0.05）。结论　DZIP1通过影响Wnt/β-catenin信号通路促进口腔鳞状细胞癌增殖、迁移和侵袭。     

丝氨酸/苏氨酸蛋白激酶通路介导的p53基因抑制口腔鳞状细胞癌增殖和侵袭的实验研究

目的 探讨人重组p53腺病毒（rAd-p53）注射液抑制口腔鳞状细胞癌增殖和侵袭的分子机制。方法 采用 rAd-p53注射液转染人舌鳞状细胞癌细胞系Tca8113,观察p53基因过表达对该细胞系增殖及侵袭能力的影响,并用蛋白免疫印迹的方法检测Ad-p53转染前后Tca8113细胞系内丝裂原激活的蛋白激酶（MAPK）、丝氨酸/苏氨酸蛋白激酶（AKT）信号通路相关蛋白,细胞周期及凋亡调控蛋白细胞周期素D1（Cydin D1）、P21、Bcl-2的表达。结果 Ad-p53 转染后显著抑制Tca8113细胞系增殖和侵袭（P<0.01）,并促进细胞凋亡（P<0.001）。蛋白免疫印迹结果显示,rAd-p53 转染后显著提高了Tca8113细胞P53和P21蛋白的表达,同时显著下调了Cydin D1、Bcl-2蛋白的表达及AKT蛋白的磷酸化（P<0.01）。结论 AKT信号通路可能是p53引起的口腔鳞癌细胞增殖和侵袭抑制的关键分子机制,Cyclin D1、P21和Bcl-2蛋白可能是AKT信号通路的下游调控基因,AKT信号通路及下游调控基因有望成为肿瘤基因治疗靶点。     

Wnt信号传导通路组成蛋白与口腔鳞状细胞癌的分化和增殖

目的研究信号传导通路组成蛋白Writ-1、β-连环蛋白（β-catenin）和腺瘤样结肠息肉病（adenomatous polyposis coli，APC）基因在口腔鳞状细胞癌中的表达，探讨它们在口腔鳞状细胞癌分化和增殖中的作用。方法免疫组织化学法检测66例不同分化程度的口腔鳞状细胞癌中Wnt-1、β-连环蛋白、APC基因及MIB-1的表达。结果37例高分化口腔鳞状细胞癌中分别有30、25和31例高表达Wnt-1、APC和β-连环蛋白，7、12和6例低表达Wnt-1、APC和β-连环蛋白；29例中、低度分化口腔鳞状细胞癌中分别有6、9和11例高表达Wnt-1、APC和β-连环蛋白，23、20和18例低表达Wnt-1、APC和β-连环蛋白；66例口腔鳞状细胞癌中MIB-1有34例低表达，32例高表达。Wnt-1、β-连环蛋白和APC的表达与MIB-1和口腔鳞状细胞癌的组织学分级差异有统计学意义（P〈0．01）。结论Wnt-1、APC和β-连环蛋白在口腔鳞状细胞癌的分化和增殖中起重要作用。     

国内口腔鳞癌患者肿瘤组织中Cyclin D1表达的meta分析

目的 探讨Cyclin D1在国人口腔鳞状细胞癌中的表达及其临床意义。方法 检索中国期刊全文数据库、中国生物医学期刊引文数据库、中文科技期刊数据库、万方和中国生物医学文献数据库,收集2000—2013年国内公开发表的有关Cyclin D1和口腔鳞状细胞癌的文献,进行meta分析。结果 最终纳入12篇病例对照研究,其中口腔鳞状细胞癌组629例,口腔正常黏膜组227例;meta分析结果:Cyclin D1在国人口腔鳞状细胞癌中的阳性表达率平均为69%,OR值及95% CI为20.51［12.50,33.66］,P＜0.000 01;Cyclin D1与口腔鳞状细胞癌淋巴结转移（P＜0.000 01）、临床分期T（P=0.01）均有相关性。结论 Cyclin D1的表达与国人口腔鳞状细胞癌的发生有关,可以考虑将其作为口腔鳞状细胞癌治疗和预后的辅助性检测指标。     

口腔鳞癌中E-钙粘蛋白和基质金属蛋白酶-1的表达与患者预后的关系

［摘要］ 目的 探讨E-钙粘蛋白（E-cadherin）和基质金属蛋白酶-1（matrix metalloproteinases-1,MMP-1）在口腔鳞状细胞癌中的表达及其相关性。方法 采用免疫组化法检测141例人口腔鳞状细胞癌组织中E-cadherin和MMP-1的表达情况。结果 与正常口腔黏膜组织相比,口腔鳞状细胞癌中E-cadherin的表达呈下降趋势,而MMP-1表达呈上升趋势（E-cadherin：543.34±103.52,260.44±67.93;MMP-1：145.64±31.53,789.96±103.42;分别是正常组织和肿瘤组织;P< 0.05）。E-cadherin和MMP-1在口腔癌中的表达与淋巴结转移有关,而与肿瘤大小和复发无关。E-cadherin和MMP-1在肿瘤组织中的表达呈负相关（r=-0.379）。结论 E-adherin表达的降低及MMP-1表达的增加与人口腔鳞状细胞癌不利的临床预后和存活率的降低密切相关。     

Poor Prognosis of Oral Squamous Cell Carcinoma Correlates With ITGA6

ObjectivesOral cancer is the ninth most common cancer worldwide and a leading cause of cancer-related death. Oral squamous cell carcinoma (OSCC) accounts for 90% of all oral cancers. Autophagy is a conserved essential catabolic process related to OSCC. The aim of this study was to elucidate diagnostic and prognostic autophagy-related biomarkers in OSCC.MethodsThe OSCC gene expression data set was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the OSCC samples and adjacent healthy tissues were identified by R software. The Human Autophagy Database was screened, which revealed 222 autophagy-related genes. The autophagy-related DEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied. Protein–protein interaction network analysis was performed in the STRING database. cytoHubba in the Cytoscape software was applied to determine the top 10 hub genes. The data set of patients with OSCC from The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic value of the 10 hub genes. The association between prognosis-related hub genes and immune infiltrates was explored.ResultsTwenty-seven autophagy-related DEGs were identified. The top 10 hub genes were CCL2, CDKN2A, CTSB, CTSD, CXCR4, ITGA6, MAP1LC3A, MAPK3, PARP1, and RAB11A. ITGA6 was identified as the most efficient biomarker. Receiver operating characteristic curve analysis indicated that ITGA6 had the highest diagnostic accuracy for OSCC (area under the curve = 0.925). ITGA6 expression was significantly related to immune infiltrates.ConclusionsThe autophagy-related gene ITGA6 might be an efficient diagnostic and prognostic biomarker in OSCC.     

MicroRNA model that can predict the prognosis of oral squamous cell carcinoma based on bioinformatics analysis

目的 通过生物信息学筛选并建立与口腔鳞状细胞癌（OSCC）患者预后相关的微小RNA（miRNA）预后模型,以期对OSCC患者进行精准的分组,提高治疗的针对性。方法 通过癌症基因组图谱（TCGA）数据库下载OSCC患者的miRNA、mRNA表达谱和临床数据。采用单因素和多因素Cox风险回归分析筛选和建立miRNA预后模型。受试者工作特征曲线（ROC）和曲线下面积（AUC）检验预后模型的性能。预测6-miRNAs靶基因,与差异mRNA取交集后行基因本体论（GO）、京都基因与基因组百科全书（KEGG）信号通路富集分析。构建蛋白互作网络（PPI）筛选中枢基因。结果 通过单因素和多因素Cox回归分析得到基于6个miRNA的预后风险模型。train组、test组和所有样品组中预测5年生存率的ROC曲线下AUC值分别为0.757、0.673、0.724。单因素和多因素Cox回归分析显示,6-miRNAs预后模型可以作为一个独立的预后因素（P<0.001）。靶基因构建PPI网络中前10个中枢基因为CCNB1、EGF、KIF23、MCM10、ITGAV、MELK、PLK4、ADCY2、CENPF、TRIP13。其中EGF和ADCY2与生存预后相关（P<0.05）。结论 6-miRNAs可有效地作为OSCC患者一种新的独立的预后模型,或可成为指导OSCC精准治疗的新方法。     

基于生物信息学分析鉴定人牙周炎牙龈组织中的关键生物标志物及相关免疫细胞浸润

目的:通过生物信息学分析鉴定牙周炎牙龈组织中的关键生物标志物和相关免疫细胞浸润,探索牙周炎的发病机制。方法:从GEO数据库下载GSE10334、GSE16134和GSE23586三个数据集,通过“limma”程序包筛选差异基因,利用STRING和Cytoscape构建蛋白互作(protein-protein interaction,PPI)网络来获取毂基因,利用CIBERSORT算法分析牙周炎和健康对照之间牙龈组织的免疫细胞浸润。结果:共筛选出129个差异表达基因,构建PPI网络后获取10个毂基因,其显著富集于趋化因子和细胞因子活性等多种细胞生理活动,和细胞因子-细胞因子受体相互作用信号通路、趋化因子信号通路、IL-17信号通路。与健康对照组相比,牙周炎牙龈组织中初始B细胞、浆细胞、初始CD4+T细胞、活化的记忆CD4+T细胞、单核细胞,M1巨噬细胞和中性粒细胞的比例更高(P<0.05)。结论:毂基因的功能分析及探究牙周炎和健康牙龈中所浸润的免疫细胞之间的差异可以为研究牙周炎的发生发展机制提供新的见解和思路。     

基于RNA-Seq分析挖掘唾液腺多形性腺瘤核心基因及通路

目的：筛选多形性腺瘤（pleomorphic adenoma,PA）与瘤旁唾液腺腺体间的差异表达基因,挖掘PA形成过程中的核心基因及通路。方法：采用RNA-Seq技术,检测5例PA患者的配对肿瘤与瘤旁唾液腺腺体,筛选2组间差异基因。运用蛋白互作数据库STRING分析预测差异基因所编码蛋白间的相互作用。筛选互作网络中的核心模块及核心基因,分析核心模块中激活的信号通路,预测上述模块与PLAG1可能的相互作用关系。RT-PCR验证核心基因在20例PA患者的配对肿瘤组织及瘤旁唾液腺中的表达。采用SPSS 20.0软件包对数据进行统计学分析。结果：共测得3810个差异基因,其中2021个下调,1789个上调。核心模块中存在PI3K-AKT信号通路、ER受体信号通路、Rap1信号通路、cGMP-PKG信号通路的激活。PLAG1可能通过PHLPP1、LRRK2、β-catenin蛋白与核心模块发生作用。RT-PCR显示,核心基因在20例PA样本及其瘤旁唾液腺组织中的差异趋势与测序结果一致,且具有统计学意义（P<0.0001）。结论：核心基因ADCY3、 ADCY5、 ADORA1、 APLN、 APP、 C5、 CCL28、 DRD2、 FPR3、 GABBR1可能在PA发生、发展过程中起着重要作用,可为预防PA复发及预后标志物筛选提供思路。PLAG1可能通过PHLPP1、LRRK2、β-catenin间接激活PI3K-AKT信号通路、ER受体信号通路、Rap1信号通路、cGMP-PKG信号通路,从而诱发PA形成。     

A combinative analysis of gene expression profiles and microRNA expression profiles identifies critical genes and microRNAs in oral lichen planus

ObjectiveOral lichen planus (OLP) is a chronic inflammatory disease but aetiology and pathogenesis has not fully elucidated. To gain insight into the mechanism of OLP, bioinformatic analysis was performed in this study.DesignGSE38616 and GSE38615 were downloaded from GEO, including 7 cases of OLP and 7 healthy controls. Differentially expressed genes (DEGs) and miRNAs (DEMs) between OLP and control were screened with package Limma of R. Potential regulatory miRNAs were screened via gene set enrichment analysis. A protein–protein interaction network was constructed for the DEGs. KEGG pathways for DEGs were revealed using Gene Set Analysis Toolkit V2.ResultsAfter DEGs and DEMs were obtained, potential regulatory miRNAs of the DEGs were revealed and only miR-362 was differentially expressed in OLP compared with DEMs. Four targets of miR-362 were SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2), vesicle-associated membrane protein 4 (VAMP4), leucine rich repeat transmembrane neuronal 4 (LRRTM4) and lysine (K)-specific demethylase5C (KDM5C). Identified DEGs were significantly enriched in olfactory transduction and ribosome pathways.ConclusionmiR-362, targeting SRGAP2 and VAMP4, may be a potential risk miRNA to regulate OLP. The findings may provide potential biomarkers for diagnosis or treatment of the disease.     

Identification of potential therapeutic target genes,key miRNAs and mechanisms in oral lichen planus by bioinformatics analysis

The study aimed to identify the potential target genes and key miRNAs as well as to explore the underlying mechanisms in the pathogenesis of oral lichen planus (OLP) by bioinformatics analysis. The microarray data of GSE38617 were downloaded from Gene Expression Omnibus (GEO) database. A total of 7 OLP and 7 normal samples were used to identify the differentially expressed genes (DEGs) and miRNAs. The DEGs were then performed functional enrichment analyses. Furthermore, DEG-miRNA network and miRNA-function network were constructed by Cytoscape software. Total 1758 DEGs (598 up- and 1160 down-regulated genes) and 40 miRNAs (17 up- and 23 down-regulated miRNAs) were selected. The up-regulated genes were related to nuclear factor-Kappa B (NF-κB) signaling pathway, while down-regulated genes were mainly enriched in the function of ribosome. Tumor necrosis factor (TNF), caspase recruitment domain family, member 11 (CARD11) and mitochondrial ribosomal protein (MRP) genes were identified in these functions. In addition, miR-302 was a hub node in DEG-miRNA network and regulated cyclin D1 (CCND1). MiR-548a-2 was the key miRNA in miRNA-function network by regulating multiple functions including ribosomal function. The NF-κB signaling pathway and ribosome function may be the pathogenic mechanisms of OLP. The genes such as TNF, CARD11, MRP genes and CCND1 may be potential therapeutic target genes in OLP. MiR-548a-2 and miR-302 may play important roles in OLP development.     

The role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis

Objectives

Oral squamous cell carcinoma (OSCC) accounts for about 90% of malignant oral lesions, and is identified as the most frequently occurring malignant tumour of oral structures. We aimed to investigate the genes and pathways related with metastasis on Turkish OSCC patients.

Materials and methods

We performed whole genome expression profiling array on an Illumina platform. A total of 24 samples with 12 OSCC and 12-paired controls that had no tumour were included in the study. Hierarchic clustering and heat map were used for data visualisation and p-values assessed to identify differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Systems (IPA) analysis were performed to consider biologic meaning of differential expression of the genes between tumour and control groups.

Results

We identified 790 probe sets, corresponding to 648 genes that were effective in separating invasive and metastatic OSCC. Consequently, we found statistically relevant expression results on extracellular matrix members on MMPs such as MMP3, MMP10, MMP1 and MMP9; on laminin such as LAMC2, LAMA3 and LAMB3; several genes in the collagen family; and also on chemokines from the inflammation process.

Conclusion

Statistically relevant expression changes for MMPs, laminins, collagens, and chemokines, which are components of the extracellular matrix and inflammation process, may be considered as a molecular biomarker for early prediction. Further studies are necessary to determine and understand the molecular mechanisms that underlie OSCC metastasis.     

长链非编码RNA基因芯片技术筛选口腔扁平苔藓唾液外泌体差异表达基因

目的研究利用基因芯片技术筛选长链非编码RNA（lncRNA）和信使RNA（mRNA）在口腔扁平苔藓（OLP）唾液外泌体中的异常表达,分析和探讨lncRNA和mRNA在OLP发生、发展中可能的分子机制。 方法收集9例OLP患者和3名健康对照者的唾液样本,分离得到样本中的外泌体。对外泌体进行纳米颗粒跟踪分析（NTA）检测、透射电子显微镜检测和外泌体特异性生物标志物的蛋白免疫印迹法（Western blot）鉴定。使用lncRNA基因表达芯片技术比较糜烂型OLP患者（EOLP组）和网纹型OLP患者（ROLP组）与健康对照者唾液外泌体中lncRNA和mRNA的表达谱,筛选得到差异表达基因并进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）信号通路富集分析。 结果NTA、透射电子显微镜和Western blot检测均证实分离得到外泌体。唾液外泌体lncRNA基因表达芯片结果显示,与对照组相比,EOLP组中有267个差异表达的lncRNA,其中上调99个、下调168个;有122个差异表达的mRNA,其中上调38个、下调84个;ROLP组中有201个差异表达的lncRNA,其中上调83个、下调118个;有86个差异表达的mRNA,其中上调32个、下调54个。两组有50个相同的差异表达mRNA和128个相同的差异表达lncRNA。GO和KEGG分析显示,差异表达基因涉及到基因转录、蛋白翻译和免疫反应等多个生物学过程。 结论本研究确定了OLP患者唾液外泌体中lncRNA和mRNA的表达谱,筛选出了与OLP相关的差异表达lncRNA和mRNA,可作为诊断和阐明OLP发病机制的重要候选者。     

Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice

ObjectivesSjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.MethodsSubmandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.ResultsMyd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)-regulated genes.ConclusionsMyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation.