scholarly journals Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jialin Qu ◽  
Li Wang ◽  
Man Jiang ◽  
Zhimin Wei ◽  
Guangming Fu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Squamous Cell ◽  
Risk Index ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Roc Curve Analysis ◽  
Clinical Prognosis

Abstract Background N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m6A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. Methods We integrated three m6A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m6A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro. Results The results of the study showed that the expression of the three m6A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression. Conclusions Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m6A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma.

scholarly journals Identification of key genes associated with progression and prognosis for lung squamous cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9086 ◽  
Author(s):  
Xiaohan Ma ◽  
Huijun Ren ◽  
Ruoyu Peng ◽  
Yi Li ◽  
Liang Ming
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Characteristic Curve ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Clinical Prognosis

Background Lung squamous cell carcinoma (LUSC) is a major subtype of lung cancer with limited therapeutic options and poor clinical prognosis. Methods Three datasets (GSE19188, GSE33532 and GSE33479) were obtained from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between LUSC and normal tissues were identified by GEO2R, and functional analysis was employed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Protein–protein interaction (PPI) and hub genes were identified via the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Hub genes were further validated in The Cancer Genome Atlas (TCGA) database. Subsequently, survival analysis was performed using the Kapla–Meier curve and Cox progression analysis. Based on univariate and multivariate Cox progression analysis, a gene signature was established to predict overall survival. Receiver operating characteristic curve was used to evaluate the prognostic value of the model. Results A total of 116 up-regulated genes and 84 down-regulated genes were identified. These DEGs were mainly enriched in the two pathways: cell cycle and p53 signaling way. According to the degree of protein nodes in the PPI network, 10 hub genes were identified. The mRNA expression levels of the 10 hub genes in LUSC were also significantly up-regulated in the TCGA database. Furthermore, a novel seven-gene signature (FLRT3, PPP2R2C, MMP3, MMP12, CAPN8, FILIP1 and SPP1) from the DEGs was constructed and acted as a significant and independent prognostic signature for LUSC. Conclusions The 10 hub genes might be tightly correlated with LUSC progression. The seven-gene signature might be an independent biomarker with a significant predictive value in LUSC overall survival.

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

scholarly journals How Long Non-Coding RNAs and MicroRNAs Mediate the Endogenous RNA Network of Head and Neck Squamous Cell Carcinoma: a Comprehensive Analysis

2018 ◽  
Vol 50 (1) ◽  
pp. 332-341 ◽  
Author(s):  
Guomiao Zhao ◽  
Yaru Fu ◽  
Zhifang Su ◽  
Rongling wu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Metastasis ◽  
Lung Squamous Cell Carcinoma ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Non Coding Rnas

Background/Aims: Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete for microRNAs (miRNAs) in cancer metastasis. Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers and rare biomarkers could predict the clinical prognosis of this disease and its therapeutic effect. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify differentially expressed mRNAs (DEmRNAs) that might be key genes. GO enrichment and protein–protein interaction (PPI) analyses were performed to identify the principal functions of the DEmRNAs. An lncRNA-miRNA-mRNA network was constructed to understand the regulatory mechanisms in HNSCC. The prognostic signatures of mRNAs, miRNAs, and lncRNAs were determined by Gene Expression Profiling Interactive Analysis (GEPIA) and using Kaplan–Meier survival curves for patients with lung squamous cell carcinoma. Results: We identified 2,023 DEmRNAs, 1,048 differentially expressed lncRNAs (DElncRNAs), and 82 differentially expressed miRNAs (DEmiRNAs). We found that eight DEmRNAs, 53 DElncRNAs, and 16 DEmiRNAs interacted in the ceRNA network. Three ceRNAs (HCG22, LINC00460 and STC2) were significantly correlated with survival. STC2 transcript levels were significantly higher in tumour tissues than in normal tissues, and the STC2 expression was slightly upregulated at different stages of HNSCC. Conclusion: LINC00460, HCG22 and STC2 exhibited aberrant levels of expression and may participate in the pathogenesis of HNSCC.

scholarly journals Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Chang Gu ◽  
Xin Shi ◽  
Wenli Qiu ◽  
Zhenyu Huang ◽  
Yan Yu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Lung Squamous Cell Carcinoma ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Occurrence Frequency ◽  
Prognostic Role ◽  
Cox Analysis

BackgroundThere have been limited treatment therapies for lung squamous cell carcinoma (LUSC). M6A-related genes may be the next therapeutic targets for LUSC. In this study, we explored the prognostic role and mutational characteristics of m6A-related genes in LUSC.MethodsLUSC gene expression data, mutational data, and corresponding clinical information were extracted from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified, and the mutation characteristics of LUSC patients were explored. Then, m6A-related genes were extracted and the correlations among the genes were detected. Finally, the prognostic roles of the genes were investigated and the nomogram model was developed. Besides, the protein–protein interaction (PPI) network was used to explore the potential interactions among the genes.ResultsIn total, there are 551 LUSC samples enrolled in our study, containing 502 LUSC tumor samples and 49 adjacent normal LUSC samples, respectively. There were 2970 upregulated DEGs and 1806 downregulated DEGs were further explored. IGF2BP1 and RBM15 had significant co-occurrence frequency (p &lt; 0.05). Besides, METTL14 and ZC3H13 or YTHDF3 also had significant co-occurrence frequency (p &lt; 0.05). All the m6A-related genes represent the positive correlation. WTAP was identified as a prognostic gene in the TCGA database while YTHDC1 and YTHDF1 were identified as prognostic genes. In multivariate Cox analysis, YTHDF1, age, pN stage, pTNM stage, and smoking were all identified as significant prognostic factors for OS.ConclusionWe investigated the expression patterns and mutational characteristics of LUSC patients and identified three potential independent prognostic m6A-related genes (WTAP, YTHDC1, and YTHDF1) for OS in LUSC patients.

scholarly journals Systematic Pan-Cancer Analysis Identifies TREM2 as an Immunological and Prognostic Biomarker

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Cheng ◽  
Xiaowei Wang ◽  
Kechao Nie ◽  
Lin Cheng ◽  
Zheyu Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Immunoglobulin Superfamily ◽  
Cancer Types ◽  
Pan Cancer

Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although increasing evidence supports a vital role for TREM2 in tumorigenesis of some cancers, no systematic pan-cancer analysis of TREM2 is available. Thus, we aimed to explore the prognostic value, and investigate the potential immunological functions, of TREM2 across 33 cancer types. Based on datasets from The Cancer Genome Atlas, and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and Human Protein Atlas, we employed an array of bioinformatics methods to explore the potential oncogenic roles of TREM2, including analyzing the relationship between TREM2 and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration of different tumors. The results show that TREM2 is highly expressed in most cancers, but present at low levels in lung cancer. Further, TREM2 is positively or negatively associated with prognosis in different cancers. Additionally, TREM2 expression was associated with TMB and MSI in 12 cancer types, while in 20 types of cancer, there was a correlation between TREM2 expression and DNA methylation. Six tumors, including breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, were screened out for further study, which demonstrated that TREM2 gene expression was negatively correlated with infiltration levels of most immune cells, but positively correlated with infiltration levels of M1 and M2 macrophages. Moreover, correlation with TREM2 expression differed according to T cell subtype. Our study reveals that TREM2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

scholarly journals Association Between Tumor Mutation Burden (TMB) and immune microenvironment in lung squamous cell carcinoma

2020 ◽  
Author(s):  
Dan Yan ◽  
Yi Chen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Wilcoxon Test ◽  
Kegg Pathways ◽  
Pathways Analysis ◽  
One Year

Abstract Background Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. And many studies have revealed high-TMB may be significantly associated with response to PD-1 and PD-L1 blockade immunotherapy.Methods The RNA-seq transcriptome profiling, simple nucleotide variation and corresponding clinicopathological information of patients with lung squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA). We classified samples into the low-TMB group and the high-TMB group based on somatic mutation data from TCGA. KEGG pathways analysis was used to analyze the enriched pathways between two groups. Wilcoxon test was used to analyze the correlation between TMB and clinical pathology. CIBERSORT was used to calculate the immune cell infiltration among different risk groups.Result Single nucleotide polymorphism (SNP), missense mutation and C > A was most common in patients with lung squamous cell carcinoma. Top 10 most common mutated genes were TTN, TP53, MUC16, CSMD3, RYR2, LRP1B, USH2A, SYNE1, ZFHX4, KMT2D. High-TMB group conferred better one-year overall survival. KEGG pathways analysis revealed that DEGs were mainly involved in regulation of lymphocyte activation, lymphocyte proliferation, leukocyte proliferation and mononuclear cell proliferation. Infiltration levels of CD8 + T cell, M1 macrophages, follicular helper T cells and activated NK cells in high-TMB group were higher than that in low-TMB group.Conclusion High TMB correlated with positive one-year survival outcomes. With the development of tumor, TMB increased gradually. TMB might influence the immune infiltrates on patients with lung squamous cell carcinoma.

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