scholarly journals Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

2021 ◽  
Vol 11 (2) ◽  
pp. 154 ◽  
Author(s):  
Talip Zengin ◽  
Tuğba Önal-Süzek
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Model ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Low Risk ◽  
Cancer Subtypes

Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed a univariate Cox model and then lasso-regularized Cox model with leave-one-out cross-validation using The Cancer Genome Atlas (TCGA) gene expression data in tumor samples. We generated 35- and 33-gene signatures for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high- and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then, we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more downregulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both up- and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. The low-risk groups of both LUAD and LUSC tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology.

scholarly journals Comprehensive profiling of genomic and transcriptomic differences between risk groups of lung adenocarcinoma and lung squamous cell carcinoma

2021 ◽  
Author(s):  
Talip Zengin ◽  
Tuğba Önal-Süzek
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Model ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Low Risk

AbstractLung cancer is the second frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma and lung squamous cell carcinoma are subtypes of non-small cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed univariate cox model and then lasso regularized cox model with leave-one-out cross-validation using TCGA gene expression data in tumor samples. We generated a 35-gene signature and a 33-gene signature for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high-risk and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more down-regulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both upregulated and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. Low-risk groups of both LUAD and LUSC, tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology.

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 The Regulators Associated With N6-Methyladenosine in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Reveal New Clinical and Prognostic Markers

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuzhen Tan ◽  
Zesong Li ◽  
Kai Li ◽  
Yingqi Li ◽  
Guosheng Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Lung Squamous Cell Carcinoma ◽  
Lung Cancers ◽  
Pathological Characteristics

N6-methyladenosine (m6A) methylation is of significant importance in the initiation and progression of tumors, but how specific genes take effect in different lung cancers still needs to be explored. The aim of this study is to analyze the correlation between the m6A RNA methylation regulators and the occurrence and development of lung cancer. The data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained through the TCGA database. We systematically analyzed the related pathological characteristics and prognostic factors by applying univariate and multivariate Cox regression, as well as LASSO Cox regression. Some of 23 m6A regulators are identified as having high expression in lung cancer. In addition, risk score has been shown to be an independent prognostic factor in lung cancer. Our research not only fully reveals that m6A regulators and clinical pathological characteristics are potentially useful with respect to survival and prognosis in different lung tumors but also can lay a theoretical root for the treatment for lung cancer—notably, to point out a new direction for the development of treatment.

scholarly journals CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

2020 ◽  
Author(s):  
Lei Li ◽  
Pengchao Zheng
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods : CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

scholarly journals CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

2020 ◽  
Author(s):  
Lei Li ◽  
Pengfei Zheng
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods: CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

scholarly journals Genetic Liability to Insomnia and Lung Cancer Risk: A Mendelian Randomization Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiayi Shen ◽  
Huaqiang Zhou ◽  
Jiaqing Liu ◽  
Yaxiong Zhang ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Confidence Interval ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Lung Squamous Cell Carcinoma ◽  
Genetic Liability

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer death worldwide, making its prevention an urgent issue. Meanwhile, the estimated prevalence of insomnia was as high as 30% globally. Research on the causal effect of insomnia on lung cancer incidence is still lacking. In this study, we aimed to assess the causality between the genetic liability to insomnia and lung cancer. We performed a two-sample Mendelian randomization analysis (inverse variance weighted) to determine the causality between the genetic liability to insomnia and lung cancer. Subgroup analysis was conducted, which included lung adenocarcinoma and lung squamous cell carcinoma. In the sensitivity analysis, we conducted heterogeneity test, MR Egger, single SNP analysis, leave-one-out analysis, and MR PRESSO. There were causalities between the genetic susceptibility to insomnia and increased incidence of lung cancer [odds ratio (95% confidence interval), 1.35 (1.14–1.59); P, &lt; 0.001], lung adenocarcinoma [odds ratio (95% confidence interval), 1.35 (1.07–1.70); P, 0.01], and lung squamous cell carcinoma [odds ratio (95% confidence interval), 1.35 (1.06–1.72), P, 0.02]. No violation of Mendelian randomization assumptions was observed in the sensitivity analysis. There was a causal relationship between the genetic susceptibility to insomnia and the lung cancer, which was also observed in lung adenocarcinoma and lung squamous cell carcinoma. The underlying mechanism remains unknown. Effective intervention and management for insomnia were recommended to improve the sleep quality and to prevent lung cancer. Moreover, regular screening for lung cancer may be beneficial for patients with insomnia.

scholarly journals The bioinformatics analysis of RIOX2 gene in lung adenocarcinoma and squamous cell carcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259447
Author(s):  
Bingqing Sun ◽  
Hongwen Zhao
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Public Health Issue ◽  
High Morbidity ◽  
Link Type

Lung cancer is characterized by high morbidity and mortality rates, and it has become an important public health issue worldwide. The occurrence and development of tumors is a multi-gene and multi-stage complex process. As an oncogene, ribosomal oxygenase 2 (RIOX2) has been associated with a variety of cancers. In this article, we analyzed the correlation between RIOX2 expression and methylation in lung cancer based on the databases including the cancer genome atlas (TCGA) (https://portal.gdc.cancer.gov/) and the gene expression omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). It was found that RIOX2 is highly expressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, whose expression is negatively correlated with its methylation level. In this regard, methylation at cg09716038, cg14773523, cg14941179, and cg22299097 had a significant negative correlation with RIOX2 expression in LUAD, whereas in LUSC, methylation at cg09716038, cg14773523, cg14941179, cg22299097, cg05451573, cg10779801, and cg23629183 is negatively correlated with RIOX2 expression. According to the analysis based on the databases, RIOX2 gene could not be considered as the independent prognostic biomarker in lung adenocarcinoma or squamous cell lung cancer. However, the molecular mechanism of RIOX2 gene in the development of lung cancer may be helpful in improving lung cancer therapy.

scholarly journals Potential Biomarkers for Predicting the Overall Survival of Lung squamous cell carcinoma: A analysis of Ferroptosis-Related lncRNAs

2021 ◽  
Author(s):  
zixuan Wu ◽  
Xuyan Huang ◽  
Min-jie Cai ◽  
Peidong Huang ◽  
Zunhui Guan
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Background In 502 Lung squamous cell carcinoma (LUSC) samples from The Cancer Genome Atlas (TCGA) datasets, the predictive significance of ferroptosis-related long non-coding RNAs (lncRNAs) was investigated. In LUSC, we meant to express how ferroptosis-associated lncRNAs interact with immune cell infiltration. Methods Gene expression enrichment was investigated using gene set enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes. The prognostic model was constructed using Lasso regression. To better understand immune cell infiltration in different risk groups and its relationship to clinical outcome, researchers analyzed by modifications in the tumor microenvironment (TME) and immunological association. The expression of lncRNA was intimately connected to that of ferroptosis, according to co-expression analyses. Ferroptosis-related lncRNAs were shown to be partially overexpressed in high-risk patients in the absence of additional clinical signs, suggesting that they may be incorporated into a prediction model to predict LUSC prognosis. GSEA revealed the immunological and tumor-related pathways in the low-risk group. Results According to TCGA, CCR and inflammation-promoting genes were considered to be significantly different between the low-risk and high-risk groups. The expression of C10orf55, AC016924.1, AL161431.1, LUCAT1, AC104248.1, and MIR3945HG were likewise different in the two risk groups. Conclusion LncRNAs linked to ferroptosis are connected to the occurrence and development of LUSC. With the use of matching prognostic models, the prognosis of LUSC patients can be predicted. In LUSC, ferroptosis-related lncRNAs and immune cell infiltration in the TME might be novel therapeutic targets that should be investigated further.

scholarly journals Development of an autophagy-related gene prognostic signature in lung adenocarcinoma and lung squamous cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8288 ◽  
Author(s):  
Jie Zhu ◽  
Min Wang ◽  
Daixing Hu
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Regression Model ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Low Risk ◽  
Prognostic Signature ◽  
Risk Patients

Purpose There is plenty of evidence showing that autophagy plays an important role in the biological process of cancer. The purpose of this study was to establish a novel autophagy-related prognostic marker for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods The mRNA microarray and clinical data in The Cancer Genome Atlas (TCGA) were analyzed by using a univariate Cox proportional regression model to select candidate autophagy-related prognostic genes. Bioinformatics analysis of gene function using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) platforms was performed. A multivariate Cox proportional regression model helped to develop a prognostic signature from the pool of candidate genes. On the basis of this prognostic signature, we could divide LUAD and LUSC patients into high-risk and low-risk groups. Further survival analysis demonstrated that high-risk patients had significantly shorter disease-free survival (DFS) than low-risk patients. The signature which contains six autophagy-related genes (EIF4EBP1, TP63, BNIP3, ATIC, ERO1A and FADD) showed good performance for predicting the survival of LUAD and LUSC patients by having a better Area Under Curves (AUC) than other clinical parameters. Its efficacy was also validated by data from the Gene Expression Omnibus (GEO) database. Conclusion Collectively, the prognostic signature we proposed is a promising biomarker for monitoring the outcomes of LUAD and LUSC.

scholarly journals Systematic Analysis of Gene Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma with a Case Study of FAM83A and FAM83B

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 886 ◽  
Author(s):  
Ling Cai ◽  
Danni Luo ◽  
Bo Yao ◽  
Donghan M. Yang ◽  
ShinYi Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Expression Data ◽  
Specific Expression

Introduction: In our previous study, we constructed a Lung Cancer Explorer (LCE) database housing lung cancer-specific expression data and clinical data from over 6700 patients in 56 studies. Methods: Using this dataset of the largest collection of lung cancer gene expression along with our meta-analysis method, we systematically interrogated the association between gene expression and overall survival as well as the expression difference between tumor and normal (adjacent non-malignant tissue) samples in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQCC). A case study for FAM83A and FAM83B was performed as a demonstration for hypothesis testing with our database. Results: We showed that the reproducibility of results across studies varied by histological subtype and analysis type. Genes and pathways unique or common to the two histological subtypes were identified and the results were integrated into LCE to facilitate user exploration. In our case study, we verified the findings from a previous study on FAM83A and FAM83B in non-small cell lung cancer. Conclusions: This study used gene expression data from a large cohort of patients to explore the molecular differences between lung ADC and SQCC.

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