scholarly journals Associations of Individual and Joint Expressions of ERCC6 and ERCC8 with Clinicopathological Parameters and Prognosis of Gastric Cancer

2020 ◽  
Author(s):  
Jing Chen ◽  
Liang Li ◽  
Li-Ping Sun ◽  
Yuan Yuan ◽  
Jing-jing Jing
Keyword(s):  
Gastric Cancer ◽  
Interaction Analysis ◽  
Excision Repair ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Double Negative ◽  
Clinical Value ◽  
Double Positive ◽  
Tissue Samples

Abstract BackgroundExcision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic disease and cancer. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.MethodsIn this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) with 109 paired GC and para-cancerous normal tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis for the exploration of the function and regulation network of ERCC6 and ERCC8 in GC.ResultsIndividual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. Protein expressed levels of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated an increased OS with higher ERCC6 protein expression and ERCC8 mRNA expression, and a decreased OS with double negative ERCC6-ERCC8 expression. Bioinformatic analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. Direct physical interactions were found between ERCC6 and ERCC8.ConclusionsIndividual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Expressed levels of ERCC6 and double negative ERCC6-ERCC8 protein, and ERCC8 mRNA were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and could regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

scholarly journals Associations of Individual and Joint Expressions of ERCC6 and ERCC8 with Clinicopathological Parameters and Prognosis of Gastric Cancer

2021 ◽  
Author(s):  
Jing Chen ◽  
Liang Li ◽  
Li-Ping Sun ◽  
Yuan Yuan ◽  
Jing-jing Jing
Keyword(s):  
Gastric Cancer ◽  
Interaction Analysis ◽  
Excision Repair ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Double Negative ◽  
Clinical Value ◽  
Double Positive ◽  
Tissue Samples

Abstract BackgroundExcision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic disease and cancer. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.MethodsIn this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) with 109 paired GC and para-cancerous normal tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis for the exploration of the function and regulation network of ERCC6 and ERCC8 in GC.ResultsIndividual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. Protein expressed levels of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated an increased OS with higher ERCC6 protein expression and ERCC8 mRNA expression, and a decreased OS with double negative ERCC6-ERCC8 expression. Bioinformatic analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. Direct physical interactions were found between ERCC6 and ERCC8.ConclusionsIndividual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Expressed levels of ERCC6 and double negative ERCC6-ERCC8 protein, and ERCC8 mRNA were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and could regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

scholarly journals Associations of individual and joint expressions of ERCC6 and ERCC8 with clinicopathological parameters and prognosis of gastric cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11791
Author(s):  
Jing Chen ◽  
Liang Li ◽  
Liping Sun ◽  
Yuan Yuan ◽  
Jingjing Jing
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Interaction Analysis ◽  
Excision Repair ◽  
Mtor Pathway ◽  
Clinicopathological Parameters ◽  
Double Negative ◽  
Tissue Samples ◽  
Gene Sets

Background Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic diseases and cancers. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear. Methods In this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) in 109 paired GC and para-cancerous normal tissue samples. The mRNA expression was detected in 36 pairs of tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis to explore the function and regulation networks of ERCC6 and ERCC8 in GC. Results Individual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. ERCC6 mRNA expression showed no difference in GC and paired tissues, while ERCC8 mRNA was significantly decreased in GC tissues. Protein expression of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated that the OS was longer when ERCC6 protein expression and ERCC8 mRNA expression increased, and double negative ERCC6-ERCC8 expression was associated with a short OS. Bioinformatics analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. KEGG pathway showed that ERCC6/ERCC8 related gene sets were mainly involved in the regulation of PI3K/AKT/mTOR pathway. Direct physical interactions were found between ERCC6 and ERCC8. Conclusions Individual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Protein expression of ERCC6, ERCC6-ERCC8, and mRNA expression of ERCC8 were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and may regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

scholarly journals Clinical Value of Serum Thrombospondin-2 Combined with CA19-9 in Early Diagnosis of Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Lanzhi Li ◽  
Jie Dong ◽  
Lei Fu ◽  
Xinhua Xia ◽  
Feng Pan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Signaling Pathways ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Gastric Tumor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cancer Tissue ◽  
Clinical Value ◽  
Healthy Control

Gastric cancer (GC) is a kind of common cancer worldwide. Too late in diagnosis results in poor prognosis of patients with GC. Thrombospondin-2 (THBS2) is a type of secreted protein that has been found to be a diagnostic biomarker in a variety of cancers. Our study aimed to uncover the clinical value of THBS2 in early detection for patients with gastric cancer. THBS2 was upregulated in gastric cancer tissue compared with normal tissue via analyzing data obtained from The Cancer Genome Atlas (TCGA) database. Additionally, the enzyme-linked immunosorbent assay revealed that the level of serum THBS2 and carcinoembryonic antigen, CA19-9, was higher dramatically in patients with early gastric cancer (EGC) than that in healthy control (HC) in addition to patients with benign gastric tumor (BGT), which suggested that THBS2 indeed associated with GC. Receiver operator characteristic (ROC) curve assay was conducted to demonstrate that serum THBS2 was similar to CA19-9 to distinguish patients with early gastric cancer from healthy control and patients with benign gastric tumor and that THBS2 combined with CA19-9 improved the detective performance of THBS2 for early gastric cancer. Furthermore, we applied the gene set enrichment analysis assay to analyze signaling pathways related to THBS2. We found that THBS2 positively controlled MAPK and WNT signaling pathways, which indicated that THBS2 might exert its functions via the pathway mentioned above. Thus, our study expounded that serum THBS2 could serve as a vital early diagnostic marker for patients with gastric cancer.

scholarly journals ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12605
Author(s):  
Tongtong Zhang ◽  
Suyang Yu ◽  
Shipeng Zhao
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Survival Curve ◽  
Enrichment Analysis ◽  
Prognostic Indicator ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
The Relationship

Background Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. Material and Methods The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. Results ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. Conclusions Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

scholarly journals Biglycan Overexpression Predicts Poor Prognosis of Gastric Cancer

2021 ◽  
Author(s):  
Xin-zhou Huang ◽  
Hui Chen ◽  
Wen-ming Song ◽  
Ying-ying Wang ◽  
Meiyuan Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Receptor Interaction ◽  
Significant Implication ◽  
Mrna Levels

Abstract Background: Biglycan (BGN) encodes an extracellular matrix (ECM) proteoglycan. However, the potential diagnostic and prognostic value of BGN in gastric cancer (GC) have not yet been reported. In this analysis, BGN expression in GC was evaluated across the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Oncomine databases, and verified using immunohistochemistry (IHC). The relationship between BGN expression and clinicopathological parameters was assessed by chi-square test and logistic regression. We analyzed the prognostic value of BGN. Then, Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in high BGN expression datasets in GC. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in GC tissues, and the correlation between BGN and infiltrating immune cells was analyzed.Results: The results showed that the mRNA levels of BGN were significantly up-regulated in GC compared with normal tissues (all P <0.001). The Kaplan-Meier plotter online database suggested that patients with high BGN expression had a poor prognosis (P=1.3e-10). In addition, using gene sets analysis, we found that pathways of bladder cancer, Wnt-signaling, TGF-beta signaling, and ECM-receptor interaction were differentially activated in high-expression BGN tissues. Furthermore, CIBERSORT analysis for the proportion of TICs revealed that macrophages M2 was positively correlated with BGN expression. Conclusions: In conclusion, BGN can be used as potential diagnostic markers of GC, and immune cell infiltration plays an important role in the occurrence and progression of GC. The finding may have significant implication for the diagnosis, prognosis and treatment of GC.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

scholarly journals Controversial T1G3 bladder cancer is the key to revealing the changes in the biological functions of bladder cancer cells

2020 ◽  
Author(s):  
Shen Pan ◽  
Yunhong Zhan ◽  
Xiaonan Chen ◽  
Bin Wu ◽  
Bitian Liu
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Interaction Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Specific Gene ◽  
Gene Sets ◽  
Bladder Cancer Cells

Abstract Background T1G3 shows a higher chance of recurrence and progression among early bladder cancer types and the available treatment option is controversial. High recurrence and progression are the problems that need to be explored and solved. Changes in the internal signals of bladder cancer cells and differential genes may be the root cause of these problems. Methods GSE120736, GSE19915, GSE19423, GSE32548 and GSE37815 datasets were obtained from Gene Expression Omnibus (GEO ) to identify differentially expressed genes (DEGs). Bladder cancer transcript data from The Cancer Genome Atlas (TCGA) were clustered into different cell-specific gene sets according to weighted gene co-expression network analysis (WGCNA). Multiple sets of databases were used for gene expression comparison, functional enrichment, and protein interaction analysis, including The Human Protein Atlas, Cancer Dependency Map, Metascape, Gene set enrichment analysis, and DisNor. Results DEGs were obtained through GEO data comparison and intersection. After WGCNA was proven to recognise cell-specific gene sets, candidate DEGs were selected and shown to be specifically expressed in cancer cells. Candidate DEGs were related to mitosis and cell cycle. Further, 12 functional candidate markers were identified from the sequencing data of 30 bladder cancer cell lines. These genes were all up-regulated and previously shown to be closely related to bladder cancer progression. Conclusions Twelve functional genes with specific differential expression in bladder cancer cells were identified. WGCNA can identify the relatively specific expression sets of different cells in bladder cancer with greater tumour heterogeneity, which provides new perspectives for future cancer research.

scholarly journals Identifying Novel Cell Glycolysis-Related Gene Signature Predictive of Overall Survival in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xin Zhao ◽  
Jiaxuan Zou ◽  
Ziwei Wang ◽  
Ge Li ◽  
Yi Lei
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Malignant Tumors ◽  
Single Gene ◽  
Univariate Analysis ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Specificity And Sensitivity

Background. Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. The prognosis of GC remains poor due to its high malignancy, high incidence of metastasis and relapse, and lack of effective treatment. The constant progress in bioinformatics and molecular biology techniques has given rise to the discovery of biomarkers with clinical value to predict the GC patients’ prognosis. However, the use of a single gene biomarker can hardly achieve the satisfactory specificity and sensitivity. Therefore, it is urgent to identify novel genetic markers to forecast the prognosis of patients with GC. Materials and Methods. In our research, data mining was applied to perform expression profile analysis of mRNAs in the 443 GC patients from The Cancer Genome Atlas (TCGA) cohort. Genes associated with the overall survival (OS) of GC were identified using univariate analysis. The prognostic predictive value of the risk factors was determined using the Kaplan-Meier survival analysis and multivariate analysis. The risk scoring system was built in TCGA dataset and validated in an independent Gene Expression Omnibus (GEO) dataset comprising 300 GC patients. Based on the median of the risk score, GC patients were grouped into high-risk and low-risk groups. Results. We identified four genes (GMPPA, GPC3, NUP50, and VCAN) that were significantly correlated with GC patients’ OS. The high-risk group showed poor prognosis, indicating that the risk score was an effective predictor for the prognosis of GC patients. Conclusion. The signature consisting of four glycolysis-related genes could be used to forecast the GC patients’ prognosis.

scholarly journals A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Zuhua Chen ◽  
Bo Liu ◽  
Minxiao Yi ◽  
Hong Qiu ◽  
Xianglin Yuan
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Dna Hypomethylation

PurposeThe exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC).MethodsThe mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters.Results5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139–0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group.ConclusionWe construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC.

scholarly journals Upregulation of GNPNAT1 Predicts Poor Prognosis and Correlates With Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenting Liu ◽  
Kaiting Jiang ◽  
Jingya Wang ◽  
Ting Mei ◽  
Min Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Cox Regression Analysis ◽  
Normal Tissues

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P &lt; 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P &lt; 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P &lt; 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P &lt; 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P &lt; 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P &lt; 0.0001), low DNA methylation (R = −0.52, P &lt; 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P &lt; 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P &lt; 0.0001), CD4+T cells (R = −0.218, P &lt; 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.

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