Identification of key genes associated with lung adenocarcinoma by bioinformatics analysis

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.

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mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

Genes ◽

10.3390/genes11030257 ◽

2020 ◽

Vol 11 (3) ◽

pp. 257 ◽

Cited By ~ 6

Author(s):

Yitong Zhang ◽

Joseph Ta-Chien Tseng ◽

I-Chia Lien ◽

Fenglan Li ◽

Wei Wu ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Lung Adenocarcinoma ◽

Tumor Necrosis Factor Receptor ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Clinical Stages ◽

Key Genes ◽

Geo Database

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.

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Identification and Validation of a Novel Immune-Related Four-lncRNA Signature for Lung Adenocarcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.639254 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jixin Wang ◽

Xiangjun Yin ◽

Yin-Qiang Zhang ◽

Xuming Ji

Keyword(s):

Gene Expression ◽

Lung Adenocarcinoma ◽

Immune Cell ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Lasso Regression ◽

Kaplan Meier

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, the prognosis of patients with which is associated with both lncRNAs and cancer immunity. In this study, we collected gene expression data of 585 LUAD patients from The Cancer Genome Atlas (TCGA) database and 605 subjects from the Gene Expression Omnibus (GEO) database. LUAD patients were divided into high and low immune-cell-infiltrated groups according to the single sample gene set enrichment analysis (ssGSEA) algorithm to identify differentially expressed genes (DEGs). Based on the 49 immune-related DE lncRNAs, a four-lncRNA prognostic signature was constructed by applying least absolute shrinkage and selection operator (LASSO) regression, univariate Cox regression, and stepwise multivariate Cox regression in sequence. Kaplan–Meier curve, ROC analysis, and the testing GEO datasets verified the effectiveness of the signature in predicting overall survival (OS). Univariate Cox regression and multivariate Cox regression suggested that the signature was an independent prognostic factor. The correlation analysis revealed that the infiltration immune cell subtypes were related to these lncRNAs.

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Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽

10.1186/s12885-021-08510-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaodong Yang ◽

Yuexin Zheng ◽

Zhihai Han ◽

Xiliang Zhang

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Killer Cell ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Normal Lung ◽

Using Data ◽

Low Expression

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

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Functions and Clinical Significance of KLRG1 in the Development of Lung Adenocarcinoma and Immunotherapy

10.21203/rs.3.rs-59360/v1 ◽

2020 ◽

Author(s):

Xiaodong Yang ◽

Yuexin Zheng ◽

Zhihai Han ◽

xiliang zhang

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Killer Cell ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Prognostic Biomarkers ◽

Normal Lung ◽

Using Data ◽

Low Expression

Abstract Background. As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 in lung adenocarcinoma (LUAD) after immune-checkpoint inhibitor therapy, as well as to explore the role of a possible KLRG1 molecular mechanism on LUAD development.Methods. Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We further established a stable LUAD cell line with KLRG1 knockdown and investigate the effect of KLRG1 knockdown on tumor cell proliferation. We also studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy.Results. The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 tumor cells. And low expression of these four factors was all associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses in LUAD patients after immunotherapy.Conclusion. Based on these findings, we infer that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD. Key pointsKLRG1 inhibits the progress of LUAD.KLRG1 had significant correlation with immunotherapy response.KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

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Overexpression of SP6 Correlates with Osteosarcoma Metastasis and Poor Prognosis

Journal of Surgical Oncology ◽

10.31487/j.jso.2020.04.06 ◽

2020 ◽

pp. 1-7

Author(s):

Dongmei Guo ◽

Chunpu Li ◽

Sicheng Wang ◽

Lili Zhao ◽

Dongmei Guo ◽

...

Keyword(s):

Gene Expression ◽

Cox Regression ◽

Excision Repair ◽

Enrichment Analysis ◽

Analysis Data ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

Roc Curve Analysis ◽

Gene Set ◽

Base Excision

Background: SP6 (Specificity protein 6) has been explored as a prospective biomarker in several cancers. In this research, the prognostic value of SP6 expression in osteosarcoma was predicted by bioinformatics analysis. Data were obtained from the Gene Expression Omnibus (GEO) database. Methods: Gene expression data and clinical materials were downloaded from the GSE21257 dataset. The mRNA expression of SP6 was compared between metastatic and non-metastatic tissues with the Wilcoxon rank-sum test, and the relationship between SP6 and clinicopathological characters was analysed using logistic regression. In addition, the correlation between SP6 and survival rate was assessed using KaplanMeier and Cox regression. Moreover, receiver operating characteristic (ROC) curve analysis was conducted to determine the prognostic merit of SP6 for osteosarcoma. The biological functions of SP6 were annotated and evaluated through gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Results: SP6 was significantly highly expressed in metastatic osteosarcoma tissues (p = 0.002). High SP6 expression showed a positive correlation with Huvos grade (OR = 6.60 for I vs. II, p = 0.028). The overall survival (OS) of the patients with high SP6 expression was significantly poorer than the low SP6 expression group (p = 0.027). The multivariate analysis revealed that SP6 expression (p = 0.002, HR = 15.40 (95% CI [2.84–83.44])) was independently correlated with OS. GSEA and GSVA showed that "spliceosome" and "base excision repair" were significantly upregulated in the high expression group of SP6. Conclusion: SP6 may serve an independent prognostic biomarker in osteosarcoma.

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Bioinformatics Analysis to Identify Key Genes and Pathways Associated with Sex Differences in Rheumatoid Arthritis

10.21203/rs.3.rs-687988/v1 ◽

2021 ◽

Author(s):

Siwei Su ◽

Wenjun Jiang ◽

Xiaoying Wang ◽

Sen Du ◽

Lu Zhou ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Hub Genes ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Ppi Networks ◽

Males And Females ◽

Key Genes

Abstract ObjectiveThis study aims to explore the key genes and investigated the different signaling pathways of rheumatoid arthritis (RA) between males and females.Data and MethodsThe gene expression data of GSE55457, GSE55584, and GSE12021 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software. Then, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of DEGs were constructed by Cytoscape 3.6.0. ResultsA total of 416 upregulated DEGs and 336 downregulated DEGs were identified in males, and 744 upregulated DEGs and 309 downregulated DEGs were identified in females.IL6, MYC, EGFR, FOS and JUN were considered as hub genes in RA pathogenesis in males, while IL6, ALB, PTPRC, CXCL8 and CCR5 were considered as hub genes in RA pathogenesis in females. ConclusionIdentified DEG may be involved in the different mechanisms of RA disease progression between males and females, and they are treated as prognostic markers or therapeutic targets for males and females. The pathogenesis mechanism of RA is sex-dependent.

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Altered Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/5533483 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Zhiqiang Wang ◽

Zhongjun Ding ◽

Yan Guan ◽

Chunhui Liu ◽

Linjun Wang ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Therapeutic Targets ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Nonobstructive Azoospermia ◽

Coexpression Analysis ◽

Qrt Pcr ◽

Key Genes

Background. The molecular mechanism of nonobstructive azoospermia (NOA) remains unclear. The aim of this study was to identify gene expression changes in NOA patients and to explore potential biomarkers and therapeutic targets. Methods. The gene expression profiles of GSE45885 and GSE145467 were collected from the Gene Expression Omnibus (GEO) database, and the differences between NOA and normal spermatogenesis were analyzed. Enrichment analysis was performed to explore biological functions for common differentially expressed genes (DEGs) in GSE45885 and GSE145467. Coexpression analysis of DEGs in GSE45885 was performed, and two modules with the highest correlation with NOA were screened. Key genes were then screened from the intersection genes of the two modules and common DEGs and PPI network. The expression of key genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Finally, through miRTarBase, miRDB, and RAID, the miRNAs were predicted to regulate key genes, respectively. Results. A total of 345 common DEGs were identified and they were mainly related to spermatogenesis, insulin signaling pathway. Coexpression analysis of DEGs in GSE45885 yielded eight modules; MEblack and MEturquoise had the highest correlation with NOA. Six genes in MEturquoise and RNF141 in MEblack were identified as key genes. qRT-PCR experiments validated the differential expression of key genes between NOA and control. Furthermore, RNF141 was regulated by the largest number of miRNAs. Conclusion. Our findings suggest that the significant change expression of key genes may be potential markers and therapeutic targets of NOA and may have some impact on the development of NOA.

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Upregulation of EMID1 accelerates to a favorable prognosis and immune infiltration in lung adenocarcinoma.

10.21203/rs.3.rs-28724/v1 ◽

2020 ◽

Author(s):

Chengrui Li ◽

Yufeng Wan ◽

Weijun Deng ◽

Fan Fei ◽

Linlin Wang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Enrichment Analysis ◽

Notch Signaling Pathway ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Rank Test ◽

Survival Status ◽

Signed Rank Test

Abstract Background Lung cancer is a kind of refractory cancer. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Although there are many ways to treat lung cancer, the survival rate of patients has not improved. Therefore, more new molecules need to be found for the diagnosis and treatment of LUAD. Methods The data from The Cancer Genome Atlas (TCGA) database were used to analyze the value of EMID1 in diagnosis and prognosis of LUAD. The relationship between clinic pathological features and EMID1 was analyzed with the Wilcoxon signed-rank test and logistic regression by R (v.3.5.1). Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential mechanism of EMID1 expression on the prognosis of LUAD. The correlation between tumor infiltrating immune cells and genes was assessed by CIBERSORT. In addition, GEPIA and Gene Expression Omnibus (GEO) database were used to verify the results. Results The decreased expression of EMID1 was significantly related to the late stage and metastasis of lung cancer. Kaplan Meier survival analysis showed that patients with low expression of EMID1 had worse prognosis than those with high expression of EMID1. Notch signaling pathway may be an important biological pathway for EMID1 to play a role in LUAD. In addition, CIBERSORT also found that the infiltration level of B cells was positively correlated with the expression of EMID1, which played an important role in the immune environment of LUAD. All results were validated in GEO and GEPIA database. Conclusion The analysis of EMID1 was helpful to understand the immune microenvironment of LUAD and improve the survival status of patients with LUAD. All the results suggested that EMID1 might be a new immune related prognostic marker of LUAD.

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FURIN correlated with immune infiltration serves as a potential biomarker in SARS-CoV-2 infection-related lung adenocarcinoma

10.21203/rs.3.rs-629424/v2 ◽

2021 ◽

Author(s):

Lianxiang Luo ◽

Manshan Li ◽

Jiating Su ◽

Xinyue Yao ◽

Hui Luo

Keyword(s):

Gene Expression ◽

Lung Adenocarcinoma ◽

Gene Expression Omnibus ◽

Poor Overall Survival ◽

Immune Infiltration ◽

Interactive Analysis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Human Protein Atlas

Abstract FURIN, as a proprotein convertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) requires FURIN to enter human cells. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma has not been clarified. Therefore, in order to explore the prognostic value and mechanism of FURIN in lung adenocarcinoma, we performed bioinformatics analysis with Oncomine, TIMER (Tumor Immune Estimation Resource), GEPIA (Gene Expression Profiling Interactive Analysis), HPA (human protein atlas), UALCAN, PrognoScan, Kaplan-Meier plotter, cBioPortal, and LinkedOmics databases. And then We used GSE44274 in the GEO (Gene Expression Omnibus) database to analyze the expression of FURIN in LUAD patients who infected with SARS-CoV. FURIN was highly expressed in lung adenocarcinoma and was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

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Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database

BioMed Research International ◽

10.1155/2020/8341097 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Long Zheng ◽

Xiaojie Dou ◽

Xiaodong Ma ◽

Wei Qu ◽

Xiaoshuang Tang

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cell Lines ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Key Genes ◽

Geo Database

Enzalutamide (ENZ) has been approved for the treatment of advanced prostate cancer (PCa), but some patients develop ENZ resistance initially or after long-term administration. Although a few key genes have been discovered by previous efforts, the complete mechanisms of ENZ resistance remain unsolved. To further identify more potential key genes and pathways in the development of ENZ resistance, we employed the GSE104935 dataset, including 5 ENZ-resistant (ENZ-R) and 5 ENZ-sensitive (ENZ-S) PCa cell lines, from the Gene Expression Omnibus (GEO) database. Integrated bioinformatics analyses were conducted, such as analysis of differentially expressed genes (DEGs), Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), and survival analysis. From these, we identified 201 DEGs (93 upregulated and 108 downregulated) and 12 hub genes (AR, ACKR3, GPER1, CCR7, NMU, NDRG1, FKBP5, NKX3-1, GAL, LPAR3, F2RL1, and PTGFR) that are potentially associated with ENZ resistance. One upregulated pathway (hedgehog pathway) and seven downregulated pathways (pathways related to androgen response, p53, estrogen response, TNF-α, TGF-β, complement, and pancreas β cells) were identified as potential key pathways involved in the occurrence of ENZ resistance. Our findings may contribute to further understanding the molecular mechanisms of ENZ resistance and provide some clues for the prevention and treatment of ENZ resistance.

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