scholarly journals Identification of Key Genes Related to Lung Squamous Cell Carcinoma Using Bioinformatics Analysis

2020 ◽  
Vol 21 (8) ◽  
pp. 2994
Author(s):  
Miaomiao Gao ◽  
Weikaixin Kong ◽  
Zhuo Huang ◽  
Zhengwei Xie

Lung squamous cell carcinoma (LUSC) is often diagnosed at the advanced stage with poor prognosis. The mechanisms of its pathogenesis and prognosis require urgent elucidation. This study was performed to screen potential biomarkers related to the occurrence, development and prognosis of LUSC to reveal unknown physiological and pathological processes. Using bioinformatics analysis, the lung squamous cell carcinoma microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs). Furthermore, PPI and WGCNA network analysis were integrated to identify the key genes closely related to the process of LUSC development. In addition, survival analysis was performed to achieve a prognostic model that accomplished good prediction accuracy. Three hundred and thirty–seven up–regulated and 119 down-regulated genes were identified, in which four genes have been found to play vital roles in LUSC development, namely CCNA2, AURKA, AURKB, and FEN1. The prognostic model contained 5 genes, which were all detrimental to prognosis. The AUC of the established prognostic model for predicting the survival of patients at 1, 3, and 5 years was 0.692, 0.722, and 0.651 in the test data, respectively. In conclusion, this study identified several biomarkers of significant interest for additional investigation of the therapies and methods of prognosis of lung squamous cell carcinoma.

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4101 ◽  
Author(s):  
Sheng Yang ◽  
Jing Sui ◽  
Geyu Liang

Background Lung cancer is considered as one of the most frequent and deadly cancers with high mortality all around the world. It is critical to find new biomarkers for early diagnosis of lung cancer, especially lung squamous cell carcinoma (LUSC). The Cancer Genome Atlas (TCGA) is a database which provides both cancer and clinical information. This study is a comprehensive analysis of a novel diagnostic biomarker for LUSC, based on TCGA. Methods and Results The present study investigated LUSC-specific key microRNAs (miRNAs) from large-scale samples in TCGA. According to exclusion criteria and inclusion criteria, the expression profiles of miRNAs with related clinical information of 332 LUSC patients were obtained. Most aberrantly expressed miRNAs were identified between tumor and normal samples. Forty-two LUSC-specific intersection miRNAs (fold change >2, p < 0.05) were obtained by an integrative computational method, among them six miRNAs were found to be aberrantly expressed concerning characteristics of patients (gender, lymphatic metastasis, patient outcome assessment) through Student t-test. Five miRNAs correlated with overall survival (log-rank p < 0.05) were obtained through the univariate Cox proportional hazards regression model and Mantel–Haenszel test. Then, five miRNAs were randomly selected to validate the expression in 47 LUSC patient tissues using quantitative real-time polymerase chain reaction. The results showed that the test findings were consistent with the TCGA findings. Also, the diagnostic value of the specific key miRNAs was determined by areas under receiver operating characteristic curves. Finally, 577 interaction mRNAs as the targets of 42 LUSC-specific intersection miRNAs were selected for further bioinformatics analysis. Conclusion This study indicates that this novel microRNA expression signature may be a useful biomarker of the diagnosis for LUSC patients, based on bioinformatics analysis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qi-Fan Yang ◽  
Di Wu ◽  
Jian Wang ◽  
Li Ba ◽  
Chen Tian ◽  
...  

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhimin Shen ◽  
Mingduan Chen ◽  
Fei Luo ◽  
Hui Xu ◽  
Peipei Zhang ◽  
...  

Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.


2020 ◽  
Vol 17 (10) ◽  
pp. 1393-1405
Author(s):  
Zeyu Liu ◽  
Yuxiang Wan ◽  
Yuqin Qiu ◽  
Xuewei Qi ◽  
Ming Yang ◽  
...  

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