创伤愈合及压力治疗过程中瘢痕动物模型转录组水平的变化研究

目的利用RNA测序技术(RNA-seq)研究创伤愈合及压力治疗过程中巴马小型猪瘢痕动物模型转录组水平的变化。方法通过背部取皮建立巴马小型猪瘢痕模型,取皮第60 d开始加压(3.4 kPa)治疗,在取皮第0、14、30、60和90 d分别提取瘢痕组织总RNA进行测序。将所得序列映射到猪参考基因组并进行转录组重建,寻找差异表达基因(DEGs),利用生物信息学方法进一步对所得DEGs进行GO分析和KEGG通路富集性分析,同时挑选部分基因用qRT-PCR进行验证。结果测序数据经过预处理,各组均有78%以上的读段能准确比对到参考序列。DEGs鉴定结果表明,压力治疗前后有568个基因差异表达,其中上调289个,下调279个。GO富集分析发现,各组DEGs主要与细胞外基质、组织发展和皮肤发展相关。KEGG富集分析表明,创伤愈合过程中各组DEGs主要富集于细胞外基质-受体相互作用、黏着斑和凋亡通路;压力治疗前后的DEGs除了富集于以上通路,还富集于MAPK和PI3K信号通路。qRT-PCR检测表明,6个DEGs的表达模式与RNA-Seq分析结果一致,证实RNA-seq结果的可靠性。结论 RNA-seq分析鉴定出创伤愈合及压力治疗过程中瘢痕动物模型的差异表达基因,为临床瘢痕的治疗研究提供实验依据。     

Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer

Developing treatment strategies for triple-negative breast cancer (TNBC) has become an important clinical challenge. Currently, taxane-based chemotherapy is one of the standard treatments for TNBC. However, determining the key factor of taxane-resistance is urgently in need for clinical treatment for breast cancer. We used GEO data to generate paclitaxel resistance in two basal-like TNBC cell lines (SUM149 and MDA-MB-468). Seventy-one common upregulated differentially expressed genes (DEGs) and 11 downregulated DEGs were found to be related to paclitaxel resistance. By constructing protein-protein interactions, 28 hub proteins with a degree cutoff criterion of ≥1 were found. Nine hub genes (COL4A6, COL4A5, IL6, PDGFA, LPAR1, FYB, IL20, IL18R1 and INHBA) are involved in important signaling pathways. We found that upregulated PDGFA and downregulated COL4A6 were significantly associated with an insensitive response to neoadjuvant paclitaxel-based therapy. A Kaplan-Meier plot was created to check the prognostic values of 11 hub DEGs in terms of recurrence-free survival. High expressions of PDGFA and LAMB3 were correlated with poor recurrence-free survival, while low levels of FYB, IL18R1, and RASGRP1 indicated poorer relapse-free survival. Our results suggest that PDGFA, COL4A6, LPAR1, FYB, COL4A5, and RASGRP1 might be candidate target genes for taxane-based therapy in basal-like TNBC.     

Identification of four novel prognosis biomarkers and potential therapeutic drugs for human colorectal cancer by bioinformatics analysis

Colorectal cancer(CRC)is one of the most deadly cancers in the world with few reliable biomarkers that have been selected into clinical guidelines for prognosis of CRC patients.In this study,mRNA microarray datasets GSE113513,GSE21510,GSE44076,and GSE32323 were obtained from the Gene Expression Omnibus(GEO)and analyzed with bioinformatics to identify hub genes in CRC development.Differentially expressed genes(DEGs)were analyzed using the GEO2 R tool.Gene ontology(GO)and KEGG analyses were performed through the DAVID database.STRING database and Cytoscape software were used to construct a protein-protein interaction(PPI)network and identify key modules and hub genes.Survival analyses of the DEGs were performed on GEPIA database.The Connectivity Map database was used to screen potential drugs.A total of 865 DEGs were identified,including 374 upregulated and 491 downregulated genes.These DEGs were mainly associated with metabolic pathways,pathways in cancer,cell cycle and so on.The PPI network was identified with 863 nodes and 5817 edges.Survival analysis revealed that HMMR,PAICS,ETFDH,and SCG2 were significantly associated with overall survival of CRC patients.And blebbistatin and sulconazole were identified as candidate drugs.In conclusion,our study found four hub genes involved in CRC,which may provide novel potential biomarkers for CRC prognosis,and two potential candidate drugs for CRC.     

Human papillomavirus infection is not associated with laryngeal squamous cell carcinoma in Taiwan

Background/PurposeTo examine whether the prevalence rate of human papillomavirus (HPV) infection in Taiwanese patients with primary laryngeal squamous cell carcinoma (LSCC) is different from that in those with a vocal polyp (VP) or vocal fold leukoplakia (VFL).MethodsThis prospective cohort study recruited 41 consecutive patients with primary LSCC and 27 and 20 patients with VP and VFL, respectively. The HPV L1 gene in surgical specimens was detected using polymerase chain reaction. High-risk HPV DNA in tissue microarray specimens was detected using in situ hybridization. Expression of p16^INK4a in tissue microarray specimens was determined through immunohistochemistry.ResultsThe prevalence of HPV L1 DNA in the LSCC group was equivalent to that in the VP and VFL groups (7.3% vs. 7.4% vs. 10.0%; P = 0.929; effect size = 0.20). High-risk HPV DNA detected using in situ hybridization was relatively rare in all groups (2.6% vs. 5.3% vs. 0.0%; P = 0.636; effect size = 0.81). The prevalence of p16^INK4a positivity was significantly lower in the LSCC group than in the VP and VFL groups (5.1% vs. 58.8% vs. 14.3%; P < 0.001). Multivariate analysis results revealed that age ≥65 years (adjusted odds ratio, 4.09; 95% confidence interval, 1.21–13.91; P = 0.024) and p16^INK4a positivity (adjusted odds ratio, 0.10; 95% confidence interval, 0.02–0.53; P = 0.006) were LSCC risk factors.ConclusionHPV infection is uncommon in Taiwanese patients with LSCC and seems not to be associated with an increased LSCC risk. Larger sample size is warranted for further study.     

Identification of key genes and pathways in castrate-resistant prostate cancer by integrated bioinformatics analysis

ObjectiveTo identify hub genes and pathways involved in castrate-resistant prostate cancer (CRPC).MethodsThe gene expression profiles of GSE70768 were downloaded from Gene Expression Omnibus (GEO) datasets. A total of 13 CRPC samples and 110 tumor samples were identified. The differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. Protein-protein interaction (PPI) network module analysis was constructed and performed in Cytoscape software. Weighted correlation network analysis (WGCNA) was conducted to determine hub genes involved in the development and progression of CRPC. The gene expression profiles of GSE80609 were used for validation.ResultsA total of 1738 DEGs were identified, consisting of 962 significantly down-regulated DEGs and 776 significantly upregulated DEGs for the subsequent analysis. GO term enrichment analysis suggested that DEGs were mainly enriched in the extracellular matrix organization, extracellular exosome, extracellular matrix, and extracellular space. KEGG pathway analysis found DEGs significantly enriched in the focal adhesion pathway. PPI network demonstrated that the top 10 hub genes were ALB, ACACB, KLK3, CDH1, IL10, ALDH1A3, KLK2, ALDH3B2, HBA1, COL1A1. Also, WGCNA identified the top 5 hub genes in the turquoise module, including MBD4, BLZF1, PIP5K2B, ZNF486, LRRC37B2. Plus, the Venn diagram demonstrated that HBA1 was the key gene in both GSE70768 and GSE80609 datasets.ConclusionsThese newly identified genes and pathways could help urologists understand the differences in the mechanism between CRPC and PCa. Besides, it might be promising targets for the treatment of CRPC.     

Clinical significance of CCNE2 protein and mRNA expression in thyroid cancer tissues

PurposeThyroid carcinoma (TC) is the most common endocrinal malignancy worldwide. Cyclin E2 (CCNE2), a member of the cyclin family, acts as a regulatory subunit of cyclin-dependent kinases (CDKs). It controls the transition of quiescent cells into the cell cycle, regulates the G1/S transition, promotes DNA replication, and activates CDK2. This study explored the role and potential molecular mechanisms of CCNE2 expression in TC tissues.Material/methodsImmunohistochemistry was used to evaluate the CCNE2 protein expression levels in TC. High-throughput data on CCNE2 in TC were obtained from RNA sequencing (RNA-seq), microarray, and literature data. The CCNE2 expression levels in TC were comprehensively assessed through an integrated analysis. Analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPIs) data facilitated the investigation of the relative molecular mechanisms of CCNE2 in TC.ResultsThe immunohistochemical experiment showed a significant increase in the expression of CCNE2 in the TC tissues. For 505 TC and 59 non-cancerous samples from RNA-seq data, the area under the curve (AUC) was 0.8016 (95% confidence interval [CI] 0.742–0.8612; p<0.001). With another 14 microarrays, the pool standard mean difference [SMD] was 1.01 (95% CI [0.82–1.19]). The pooled SMD of CCNE2 was 1.12 (95% CI [0.60–1.64]), and the AUC was 0.87 (95% CI [0.84–0.90]) for 1157 TC samples and 366 non-cancerous thyroid samples from all possible sources. Nine hub genes were upregulated in TC.ConclusionsA high expression of CCNE2 may lead to carcinogenesis and the development of TC.     

Using microarray analysis to identify genes and pathways that regulate fetal hemoglobin levels

Increased levels of fetal hemoglobin (HbF: α2γ2) can ameliorate the clinical severity of the β-hemoglobinopathies. Microarray analysis represents a powerful approach to identify novel genetic factors regulating the γ-globin gene. Gene expression profiling was previously performed on 14 individuals with high or normal HbF levels to identify the genetic factors that control γ-globin gene expression. To obtain more accurate and reliable results, our results were combined with public microarray dataset GSE22109 deposited in the Gene Expression Omnibus database. Annotation of case versus control samples was taken directly from the microarray documentation. The differentially expressed genes (DEGs) were obtained and were deeply analyzed by bioinformatics methods. Combined with our own chip expression data, potential genes HBE1, TFRC, and CSF2 were selected out for subsequent qRT-PCR validation. A total of 184 DEGs were identified from GSE22109 and the protein–protein interaction network was constructed. Gene set enrichment analysis showed that the hematopoietic cell lineage pathway overlaps in the two datasets. HBE1, CSF2, and TFRC were confirmed by qRT-PCR. Our results suggest novel candidate genes and pathways associated with the γ-globin gene expression.     

Integrin α7 Binds Tissue Inhibitor of Metalloproteinase 3 to Suppress Growth of Prostate Cancer Cells

Integrin α7 (ITGA7) is a tumor-suppressor gene that is critical for suppressing the growth of malignant tumors; however, the mechanisms allowing ITGA7 to suppress the growth of cancer cells remain unclear. Herein, we show that ITGA7 binds to tissue inhibitor of metalloproteinase 3 (TIMP3) in prostate cancer cells. The ITGA7-TIMP3 binding led to a decreased protein level of tumor necrosis factor α, cytoplasmic translocation of NF-κB, and down-regulation of cyclin D1. These changes led to an accumulation of cells in G₀/G₁ and a dramatic suppression of cell growth. Knocking down TIMP3 or ITGA7/TIMP3 binding interference largely abrogated the signaling changes induced by ITGA7, whereas a mutant ITGA7 lacking TIMP3 binding activity had no tumor-suppressor activity. Interestingly, knocking down ITGA7 ligand laminin β1 enhanced ITGA7-TIMP3 signaling and the downstream tumor-suppressor activity, suggesting the existence of a counterbalancing role between extracellular matrix and integrin signaling. As a result, this report demonstrates a novel and critical signaling mechanism of ITGA7, through the TIMP3/NF-κB/cyclin D1 pathway.Integrin α7 (ITGA7) is a member of the extracellular matrix binding proteins. As a major class of cell adhesion molecules in mammalian cells, integrins are involved in many cellular processes, including development, immune responses, leukocyte trafficking, and hemostasis.¹ The integrin superfamily consists of 24 members, each of which mediates a unique function in mammals. The regulation of integrin expression is critical for certain aspects of tissue differentiation and regeneration (eg, keratinocyte differentiation, hair follicle formation, and skeletal muscle development),^2–4 and abnormal integrin expression is associated with several human diseases (eg, muscular dystrophy, Glanzmann’s thrombasthenia, and congenital cardiac myopathy).^4–6ITGA7 forms a heterodimer with integrin β1 in the plasma membrane and is responsible for communication between the extracellular matrix and cells.⁷ Itga7-deficient mice display significant hyperplasia and hypertrophy of arteries and arterioles and a malformation of skeletal muscles.^4,8 Recent mutational analysis revealed ITGA7 mutations in prostate cancer, hepatocellular carcinoma, soft tissue leiomyosarcoma, and glioblastoma multiforme, with frequencies ranging from 25% to 83%.⁹ Many of these mutations resulted in truncation, microdeletion, or frameshift of the protein. Interestingly, patients with prostate cancer or hepatocellular carcinoma harboring ITGA7 mutations also had a higher rate of clinical relapse.A meta-analysis of previously published microarray data^10–15 indicated that ITGA7 was down-regulated in nonmetastatic prostate cancer and leiomyosarcoma, but the magnitude of the down-regulation was larger in metastatic cancers. Also, prostate cancer and soft tissue leiomyosarcoma, with focal or no ITGA7 expression, were associated with a shorter metastasis-free survival time. The forced expression of normal ITGA7 in prostate cancer and leiomyosarcoma cell lines suppressed tumor growth and cancer cell migration in vitro. A mouse model of PC3 and DU145 xenograft prostate tumors showed a dramatic reduction in tumor volume, metastatic rate, and mortality rate when ITGA7 expression was restored. However, the molecular mechanism of ITGA7-mediated tumor-suppressor activity remains unclear. Herein, we report that the tissue inhibitor of metalloproteinase 3 (TIMP3), a matrix proteinase and a tumor suppressor, interacts with the C-terminus of ITGA7. We further show that the activation of ITGA7 leads to redistribution of NF-κB to the cytoplasm, the down-regulation of cyclin D1, and cell growth arrest.     

Brief Exercises Affect Gene Expression in Circulating Monocytes

We aimed to give a systematic hypothesis on the functions of exercise on circulating monocytes by identifying a discrete set of genes in circulating monocytes that were altered by exercise. The microarray expression profile of GSE51835 was downloaded from gene expression omnibus (GEO) database for the identification of differentially expressed genes (DEGs) using limma and affy packages in R language. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for DEGs, followed by the construction of co‐expression network and protein–protein interaction (PPI) network. The top 10 nodes in PPI network were screened, and subnetwork was constructed for the key genes identification. Totally, 35 DEGs, including 2 upregulated genes and 33 downregulated genes, were identified. The enriched GO terms were mainly linked to immune response and defence response, and the enriched KEGG pathways were mainly associated with natural killer cell‐mediated cytotoxicity and graft‐versus‐host disease. Dual‐specificity phosphatase 2 (DUSP2) was identified as a key node in the co‐expression network. In the PPI network, CD247 module (CD247), chemokine (C‐X‐C motif) receptor 4 (CXCR4), granzyme B (GZMB) and perforin 1 (PRF1) were identified as key nodes. An important interaction, GZMB/PRF1, was detected. Five key genes, including DUSP2, CD247, CXCR4, GZMB and PRF1, and an interaction of GZMB/PRF1, were significant factors in the immune processes of circulating monocytes, which might be regulated by brief exercises, leading to the enhancement of immune function.     

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real‐time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440‐13_c.1440‐1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin.     

Integrated bioinformatics analysis for differentially expressed genes and signaling pathways identification in gastric cancer

Background: Gastric cancer (GC) has a high mortality rate in cancer-related deaths worldwide. Currently, the pathogenesis of gastric cancer progression remains unclear. Here, we identified several vital candidate genes related to gastric cancer development and revealed the potential pathogenic mechanisms using integrated bioinformatics analysis.Methods: Two microarray datasets from Gene Expression Omnibus (GEO) database integrated. Limma package was used to analyze differentially expressed genes (DEGs) between GC and matched normal specimens. DAVID was utilized to conduct Gene ontology (GO) and KEGG enrichment analysis. The relative expression of OLFM4, IGF2BP3, CLDN1 and MMP1were analyzed based on TCGA database provided by UALCAN. Western blot and quantitative real time PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines, respectively.Results: We downloaded the expression profiles of {"type":"entrez-geo","attrs":{"text":"GSE103236","term_id":"103236"}}GSE103236 and {"type":"entrez-geo","attrs":{"text":"GSE118897","term_id":"118897"}}GSE118897 from the Gene Expression Omnibus (GEO) database. Two integrated microarray datasets were used to obtain differentially expressed genes (DEGs), and bioinformatics methods were used for in-depth analysis. After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis, we identified 61 DEGs in common, of which the expression of 34 genes were elevated and 27 genes were decreased. GO analysis displayed that the biological functions of DEGs mainly focused on negative regulation of growth, fatty acid binding, cellular response to zinc ion and calcium-independent cell-cell adhesion. KEGG pathway analysis demonstrated that these DEGs mainly related to the Wnt and tumor signaling pathway. Interestingly, we found 4 genes were most significantly upregulated in the DEGs, which were OLFM4, IGF2BP3, CLDN1 and MMP1. Then, we confirmed the upregulation of these genes in STAD based on sample types. In the final, western blot and qRT-PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines.Conclusion: In our study, using integrated bioinformatics to screen DEGs in gastric cancer could benefit us for understanding the pathogenic mechanism underlying gastric cancer progression. Meanwhile, we also identified four significantly upregulated genes in DEGs from both two datasets, which might be used as the biomarkers for early diagnosis and prevention of gastric cancer.     

Potential Impact of a Microarray-Based Nucleic Acid Assay for Rapid Detection of Gram-Negative Bacteria and Resistance Markers in Positive Blood Cultures

We evaluated the Verigene Gram-negative blood culture (BC-GN) test, a microarray that detects Gram-negative bacteria and several resistance genes. A total of 102 positive blood cultures were tested, and the BC-GN test correctly identified 97.9% of the isolates within its panel. Resistance genes (CTX-M, KPC, VIM, and OXA genes) were detected in 29.8% of the isolates, with positive predictive values of 95.8% (95% confidence interval [CI], 87.7% to 98.9%) in Enterobacteriaceae and 100% (95% CI, 75.9% to 100%) in Pseudomonas aeruginosa and negative predictive values of 100% (95% CI, 93.9% to 100%) and 78.6% (95% CI, 51.0% to 93.6%), respectively.     

Familial brain arteriovenous malformation maps to 5p13–q14, 15q11–q13 or 18p11: Linkage analysis with clipped fingernail DNA on high-density SNP array

Familial arteriovenous malformations (AVM) in the brain is a very rare disease. It is defined as its occurrence in two or more relatives (up to third-degree relatives) in a family without any associated disorders, such as hereditary hemorrhagic telangiectasia. We encountered a Japanese family with brain AVM in which four affected members in four successive generations were observed. One DNA sample extracted from leukocytes of the proband and ten DNA samples from clipped finger nails of other members were available. A genome-wide linkage analysis was performed on this pedigree using Affymetrix GeneCip 10K 2.0 Xba Array and MERLIN software. We obtained sufficient performance of SNP genotyping in the fingernail samples with the mean SNP call rate of 92.49%, and identified 18 regions with positive LOD scores. Haplotype and linkage analyses with microsatellite markers at these regions confirmed three possible disease-responsible regions, i.e., 5p13.2–q14.1, 15q11.2–q13.1 and 18p11.32–p11.22. Sequence analysis was conducted for ten selected candidate genes at 5p13.2–q14.1, such as MAP3K1, DAB2, OCLN, FGF10, ESM1, ITGA1, ITGA2, EGFLAM, ERBB2IP, and PIK3R1, but no causative genetic alteration was detected. This is the first experience of adoption of fingernail DNA to genome-wide, high-density SNP microarray analysis, showing candidate brain AVM susceptible regions.     

Differential expression and distribution of epithelial adhesion molecules in non-small cell lung cancer and normal bronchus

BACKGROUND: Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis. AIM: To screen for altered expression of epithelial adhesion genes in lung cancer development. METHODS: Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels. RESULTS: 43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion-that is, integrin alpha3 (ITGA3), integrin beta4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell-matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell-cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas. CONCLUSIONS: Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested.     

Gene expression profiling analysis of lung adenocarcinoma

The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The {"type":"entrez-geo","attrs":{"text":"GSE2514","term_id":"2514"}}GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.