scholarly journals Significance of mucin type glucosaminyl (N-acetyl) transferase 3 expression in lung squamous cell carcinoma

2021 ◽  
Author(s):  
Yu-Jun Chen ◽  
Li Gao ◽  
Rui Zhang ◽  
Gang Chen ◽  
Zhen-bo Feng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Methylation Level ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Genetic Mutation ◽  
Functional Enrichment ◽  
Standard Mean Difference

Abstract Background: The clinical significance and role of glycan synthase glucosamine (N-acetyl) transferase 3 (GCNT3) has not been investigated in lung squamous cell carcinoma (LUSC).Materials & Methods: In the present study, multiple detection technologies including tissue microarrays, external microarrays and RNA-seq were adopted for evaluating the clinic-pathological significance of GCNT3 in 1632 LUSC samples and 1478 non-cancer samples. Standard mean difference and hazard ratio value were calculated from all included datasets for assessing differential expression and prognostic value of GCNT3 in LUSC. The molecular basis underlying GCNT3 in LUSC was also explored through methylation level, genetic mutation and functional enrichment analysis of GCNT3-correlated genes in LUSC. Results: GCNT3 was obviously upregulated in LUSC samples. GCNT3 overexpression exerted unfavorable impact on the progression-free survival and overall survival of LUSC patients from GSE29013. The mRNA expression of GCNT3 was negatively correlated with methylation level of GCNT3 in LUSC and the predominant type of genetic alteration for GCNT3 in LUSC was mRNA high. Genes correlated with GCNT3 in LUSC mainly assembled in pathways such as adherens junction, p53 signaling pathway, protein digestion and absorption pathway. Conclusions: In conclusion, overexpressed GCNT3 had clinical potential as therapeutic target for LUSC.

Mine TCGA Database for Tumor Microenvironment-Related Genes of Prognostic value in lung squamous cell carcinoma

2020 ◽  
Author(s):  
Xiao Chen ◽  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiao Liu ◽  
Xi-Jia Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hub Genes

Abstract Background: Tumor microenvironment (TME) plays a significant role in the development of cancer. However, the roles of TME in lung squamous cell carcinoma (LUSC) are not well studied. In our study, we aimed to identify differentially expressed tumor microenvironment-related genes as biomarker for predicting the prognosis of LUSC.Methods: We combined The Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissue using Expression data (ESTIMATE) datasets to identified differentially expressed genes in lung squamous cell carcinoma microenvironment. Then, functional enrichment analysis and protein-protein interaction (PPI) network were conducted. The top six genes in the PPI network were regarded as tumor microenvironment-related hub genes. Finally, the relationship between hub genes and tumor-infiltrating immune cells was deciphered using TIMER.Results: Our study revealed that immune and stromal scores are associated with specific clinicopathologic variables in LUSC. These variables include gender, age, distant metastasis and prognosis. In addition, a total of 874 upregulated and 72 downregulated genes were identified. Functional enrichment analysis demonstrated a correlation between DEGs and the tumor microenvironment, tumor immune cells differentiation and activation. C3AR1, CSF1R, CCL2, CCR1, TYROBP, CD14were selected as the hub genes. A positive correlation was obtained between the expression of hub genes and the abundance of six immune cells.Conclusions: The results of the present study showed that ESTIMATE algorithm-based stromal and immune scores may be a reference indicator of cancer prognosis. We identified five TME-related genes, which could be used to predict the prognosis of LUSC patients.

scholarly journals Clinical Value and Potential Mechanism of miRNA-33a-5p in Lung Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Xiang-Ming Wang ◽  
Shang-Wei Chen ◽  
Gang Chen ◽  
Hua-Fu Zhou ◽  
Ting-Qing Gan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Summary Receiver Operating Characteristic ◽  
Potential Target ◽  
Standard Mean Difference

This study is aimed at thoroughly exploring the expression status, clinical significance, and underlying molecular mechanism of miRNA-33a-5p in lung squamous cell carcinoma (LUSC). Here, we detected miRNA-33a-5p in 20 samples from patients with LUSCs and 20 matching non-LUSC specimens by in-house quantitative real-time PCR (RT-qPCR). Relationship between miRNA-33a-5p expression and clinicopathological traits was investigated from materials derived from miRNA sequencing and miRNA microarrays. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to evaluate the integrated expression value of miRNA-33a-5p in LUSC. Twelve online platforms were applied to select potential target genes of miRNA-33a-5p. The differentially expressed genes (DEGs) of LUSC and the candidate target genes of miRNA-33a-5p were overlapped to acquire a set of specific genes for further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network. miRNA-33a-5p overexpressed in LUSC was supported by 706 LUSC and 261 non-LUSC samples gathering from RT-qPCR, miRNA-seq, and public miRNA microarrays. The pooled SMD was 0.56 (95% CI: -0.01-1.05), and the area under the curve (AUC) of the SROC was 0.78 (95% CI: 0.74-0.82). A total of 240 genes were identified as potential target genes of miRNA-33a-5p for functional enrichment analyses; the results suggested that these target genes may participate in several vital biological processes that promote the proliferation and progression of LUSC. miRNA-33a-5p may play an essential role in the occurrence and development of LUSC by targeting hub genes (ETS1, EDNRB, CYR61, and LRRK2) derived from the PPI network. In summary, our results indicated that miRNA-33a-5p may contribute as a prospective therapeutic target in LUSC.

scholarly journals Ferroptosis-associated gene SLC7A11 is upregulated in NSCLC and correlated with patient’s poor prognosis: An integrated bioinformatics analysis

Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 106-116
Author(s):  
He Huang ◽  
Juan Liu ◽  
Haiyan Wu ◽  
Fang Liu ◽  
Xiaoxi Zhou
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Kegg Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Progression Free Survival ◽  
Ppi Network ◽  
Free Survival ◽  
Synonymous Substitutions

Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferroptosis pathway.

scholarly journals Immune Infiltration Landscape in Lung Squamous Cell Carcinoma Implications

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Jungang Zhao ◽  
Wenming Bao ◽  
Weiyang Cai
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clustering Analysis ◽  
Immune Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Immune Microenvironment

Intrinsic cancer cells and the tumor-infiltrating immune cells (TIICs) recruited to the immune microenvironment define the malignant phenotype of lung squamous cell carcinoma (LUSC). Understanding more about the immune microenvironment of LUSC enables the selection of high-risk patients who would derive benefit from immunotherapy. Based on large public LUSC cohorts obtained from TCGA and GEO datasets, 22 types of infiltrating immune cell subgroups were evaluated by CIBERSORT. Meta-analysis, principal component analysis (PCA), single-sample gene set enrichment analysis (ssGSEA), and hierarchical clustering analysis were used to evaluate specific immune responses of LUSC. The distribution of TIICs of LUSC was entirely different from normal. TIIC subpopulations were also found to be closely associated with clinical features and molecular subtypes. Unsupervised clustering analysis revealed that three distinct TIIC subgroups existed with different survival patterns. TIICs are extensively implicated in the pathogenesis and development of LUSC. Characterizing the composition of TIICs influences the metabolism, pathological stage, and survival of tumor patients. It is hoped that this immune landscape could provide a more accurate understanding of the development and immunotherapy of LUSC.

scholarly journals Competitive Endogenous RNA Network Construction and Comparison of Lung Squamous Cell Carcinoma in Smokers and Nonsmokers

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yan Yao ◽  
Tingting Zhang ◽  
Lingyu Qi ◽  
Ruijuan Liu ◽  
Gongxi Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Differential Expression Analysis ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cerna Network

Background. Lung squamous cell carcinoma (LUSC) is a subtype of highly malignant lung cancer with poor prognosis, for which smoking is the main risk factor. However, the underlying genetic and molecular mechanisms of smoking-related LUSC remain largely unknown. Methods. We mined existing LUSC-related mRNA, miRNA, and lncRNA transcriptome data and corresponding clinical data from The Cancer Genome Atlas (TCGA) database and divided them into smoking and nonsmoking groups, followed by differential expression analysis. Functional enrichment analysis of the unique differentially expressed mRNAs of the two groups was performed using the DAVID database. Subsequently, the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network of LUSC in smoking and nonsmoking groups was constructed. Finally, survival analyses were performed to determine the effects of differentially expressed lncRNAs/mRNAs/miRNAs that were involved in the ceRNA network on overall survival and to discover the hub genes. Results. A total of 1696 lncRNAs, 125 miRNAs, and 3246 mRNAs and 1784 lncRNAs, 96 miRNAs, and 3229 mRNAs with differentially expressed profiles were identified in the smoking and nonsmoking groups, respectively. The ceRNA network and survival analysis revealed four lncRNAs (LINC00466, DLX6-AS1, LINC00261, and AGBL1), one miRNA (hsa-mir-210), and two mRNAs (CITED2 and ENPP4), with the potential as biomarkers for smoking-related LUSC diagnosis and prognosis. Conclusion. Taken together, our research has identified the differences in the ceRNA regulatory networks between smoking and nonsmoking LUSC, which could lay the foundation for future clinical research.

scholarly journals Human sperm-associated antigen 4 as a potential prognostic biomarker of lung squamous cell carcinoma

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110328
Author(s):  
Yongheng Wang ◽  
Yao Tang ◽  
Jianhui Li ◽  
Danfang Wang ◽  
Wenhan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Tumors ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Tissue Samples

Objective Lung cancer (LC) is one of the most prevalent malignant tumors worldwide. As a subtype of LC, lung squamous cell carcinoma (LUSC) has a 5-year survival rate of less than 15%. In this study, we aimed to evaluate the prognostic value of a glycolysis-related gene signature in LUSC patients. Methods We obtained RNA-Seq data from The Cancer Genome Atlas (TCGA) database. Prognosis-related genes were screened out by Gene Set Enrichment Analysis (GSEA) and Cox proportional regression models. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the mRNA expression levels in relevant tissues. Results We found that sperm-associated antigen 4 (SPAG4) overexpression was an independent risk factor for overall survival (OS) in LUSC. Patients with high-risk scores had higher mortality rates than those with low-risk scores. Moreover, by using RT-qPCR, we validated that SPAG4 mRNA was overexpressed in LUSC tissue samples compared with their paired para-cancerous histological normal tissues. Conclusions Analysis of aberrantly overexpressed SPAG4 may provide a further useful approach to complement existing methods and predict prognosis in LUSC patients.

scholarly journals The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

2022 ◽  
Author(s):  
Wan-Ying Huang ◽  
Jing-Xiao Li ◽  
Zhi-Guang Huang ◽  
Rong-Quan He ◽  
Shang-Wei Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Functional Enrichment ◽  
Clinical Parameters ◽  
Downstream Targets ◽  
Forkhead Box ◽  
Forkhead Box M1 ◽  
Standard Mean Difference ◽  
High Discrimination

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) ranks the sixth in mortality rates in cancers due to a lack of a specific target of diagnosis and treatment in the early stages. Although Forkhead box M1 (FOXM1) has been reported to be differentially expressed in ESCC, its clinical role and function in ESCC remained unclarified.MethodsData from our hospital and public databases (n = 1906) were combined to estimate how FOXM1 overexpression showed its discriminatory ability between ESCC and non-ESCC esophageal tissues. Downstream targets of FOXM1 were predicted by using Cistrome database. Functional enrichment analyses were performed to explore the potential signaling pathways related to FOXM1 in ESCC. Based on the available clinical parameters, we investigated the prognosis potential of FOXM1 and its targets.ResultsThe pooled standard mean difference (SMD) for FOXM1 is 2.62 (95% CI: 2.08–3.16), indicating that FOXM1 is upregulated in ESCC. FOXM1 has an extremely high discrimination potential in ESCC because the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) is 0.99 (95% CI: 0.97–0.99). A total of 168 downstream targets were identified, and nine hub genes were screened from them. We found that FOXM1 and its targets were significantly enriched in the cell cycle. Additionally, the correlation between FOXM1 and clinical parameters had not been observed, except for age.ConclusionsFOXM1 is upregulated in ESCC and has an extremely high discrimination potential in ESCC.

scholarly journals Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of esophageal squamous cell carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingdi Liu ◽  
Faping Li ◽  
Bin Liu ◽  
Yongping Jian ◽  
Dan Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Risk Model ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment

Abstract Background As a complex system participating in tumor development and progression, the tumor microenvironment was poorly understood in esophageal cancer especially squamous cell carcinoma (ESCC). Methods ESTIMATE algorithm is used to investigate tumor-infiltrating immune cells and prognostic genes which were associated with the tumor microenvironment in ESCC. Results Based on the immune and stromal scores, ESCC samples were divided into high and low score groups and 299 overlapping differentially expressed genes were identified. Functional enrichment analysis showed that these genes were mainly involved in muscle-related function. Prognostic genes including COL9A3, GFRA2, and VSIG4 were used to establish a risk prediction model using Cox regression analyses. Then multivariate analysis showed that COL9A3 was an independent discriminator of a better prognosis. Kaplan–Meier survival analysis showed that the expression of COL9A3 was significantly correlated with the overall survival of ESCC patients. The area under the curve for the risk model in predicting 1- and 3- year survival rates were 0.660 and 0.942, respectively. The risk score was negatively correlated with plasma cells, while positively correlated with the proportions of activated CD4 memory T cells, M1 Macrophages and M2 Macrophages (p < 0.001 for each comparison). Gene set enrichment analysis suggested that both immune response and immune system process gene sets were significantly enriched in high-risk group. Conclusions Our study provided a comprehensive understanding of the TME in ESCC patients. The establishment of the risk model is valuable for the early identification of high-risk patients to facilitate individualized treatment and improve the possibility of immunotherapy response.

scholarly journals Screening and Identification of Potential Biomarkers Associated with Cutaneous Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Wenxing Su ◽  
Biao Huang ◽  
Qingyi Zhang ◽  
Wei Han ◽  
Lu An ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Hub Genes

Abstract Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with non-melanoma skin cancers (NMSC). However, unclear pathogenesis of cSCC limits the application of molecular targeted therapy. We downloaded three microarray data (GSE2503, GSE45164 and GSE66359) from Gene Expression Omnibus (GEO) and screened out their common difference genes between tumor and non-tumor tissues. Functional enrichment analysis was performed using DAVID. The STRING online website was used to construct a protein-protein interaction network (PPI), and then Cytoscape performed module analysis and degree calculation.A total of 146 DEGs was identified with significant differences, including 113 up-regulated genes and 33 down-regulated genes. The enriched functions and pathways of the DEGs include microtubule-based movement, ATP binding, cell cycle, p53 signaling pathway, oocyte meiosis and PLK1 signaling events. Nine hub genes were identified, namely CDK1, AURKA, RRM2, CENPE, CCNB1, KIAA0101, ZWINT, TOP2A, ASPM. The differential expression of these genes has been verified in other data sets. By integrated bioinformatic analysis, the hub genes identified in this study elucidated the molecular mechanism of the pathogenesis and progression of cSCC, and are expected to become future biomarkers or therapeutic targets.

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