scholarly journals COL1A1 is a prognostic biomarker and correlated with immune infiltrates in lung cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11145
Author(s):  
Qishun Geng ◽  
Zhibo Shen ◽  
Lifeng Li ◽  
Jie Zhao
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Dendritic Cell ◽  
Cd4 T Cells ◽  
Malignant Tumors ◽  
Functional Enrichment ◽  
Expression Level ◽  
Normal Lung ◽  
Hub Genes ◽  
Clinical Prognosis

Objective Lung cancer (LC) is one of the top ten malignant tumors and the first leading cause of cancer-related death among both men and women worldwide. It is imperative to identify immune-related biomarkers for early LC diagnosis and treatment. Methods Three Gene Expression Omnibus (GEO) datasets were selected to acquire the differentially expressed genes(DEGs) between LC and normal lung samples through GEO2R tools of NCBI. To identify hub genes, the DEGs were performed functional enrichment analysis, the protein–protein interaction (PPI) network construction, and Lasso regression. Then, a nomogram was constructed to predict the prognosis of patients with carcinoma based on hub genes. We further evaluated the influence of COL1A1 on clinical prognosis using GSE3141, GSE31210, and TCGA database. Also, the correlations between COL1A1 and cancer immune infiltrates and the B7-CD28 family was investigated via TIMER and GEPIA. Further analysis of immunohistochemistry shown that the COL1A1 expression level is positively correlated with CD276 expression level. Results By difference analysis, there were 340 DEGs between LC and normal lung samples. Then, we picked out seven hub genes, which were identified as components of the risk signature to divide LC into low and high-risk groups. Among them, the expression of COL1A1 is highly correlated with overall survival(OS) and progression-free survival (PFS) (p < 0.05). Importantly, there is a moderate to strong positive relationships between COL1A1 expression level and infiltration level of CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level. Conclusion These findings suggest that COL1A1 is correlated with prognosis and immune infiltrating levels, including CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level, indicating COL1A1 can be a potential immunity-related biomarker and therapeutic target in LC.

scholarly journals The Expression and Prognostic Role of Peroxiredoxins in Lung Cancer

2019 ◽  
Author(s):  
Ben Li ◽  
Bo Zhang ◽  
Qiong Wu ◽  
Xinming Chen ◽  
Xiang Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Expression Level ◽  
Normal Lung ◽  
Lung Cells ◽  
Analysis Tool

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

scholarly journals FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8654
Author(s):  
Kai Yuan ◽  
Yanyan Feng ◽  
Hesong Wang ◽  
Lu Zhao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Lung Adenocarcinoma ◽  
T Cell Activation ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
High Expression ◽  
Expression Level ◽  
High Expression Level

Lung cancer is the most common malignant tumor, accounting for 25% of cancer-related deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8+ T cells, macrophages, B cells, and CD4+ T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8+ T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes.

Integrated computational analysis revealed hub genes in lung adenocarcinoma

2021 ◽  
Author(s):  
Muhammad Jamal ◽  
Abdul Saboor Khan ◽  
Hina Iqbal Bangash ◽  
Tian Xie ◽  
Tianbao Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Survival Analysis ◽  
Differentially Expressed Genes ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Normal Lung ◽  
Hub Genes ◽  
Altered Expression ◽  
Study Gene Expression

Abstract Background Lung cancer (LUCA) is the leading cause of cancer-related morbidities and mortalities globally. Despite the recent advancements in lung cancer research, understanding of the molecular mechanism underlying LUCA tumorigenesis and prognosis remains suboptimal. This study aims to identify the candidate biomarkers and therapeutic genes in lung cancer. Methods In this study, gene expression profiles of GSE30219, GSE33532, GSE32863 and GSE43458 were downloaded from GEO. The differentially expressed genes (DEGs) in LUAD tissue and normal lung tissue with a p-value < 0.05 and a |log fold change (FC)| >1.0 were identified by GEO2R. For functional enrichment analysis of these DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed with KOBAS and DAVID tools. Next, the candidate hub genes were filtered out with Cytoscape using CytoHubba plugin. These hub genes were validated by (the Cancer Genome Atlas) TCGA-based gene expression analysis, protein-protein network interaction (PPI) analysis, survival analysis. Moreover, the expression of these genes in cancer and normal tissue was assessed in the Human Protein Atlas (HPA) database. In addition, miRNA network of the hub genes was constructed. Finally, DGIdb database was used to check the drug-targeting potentials of the hub genes. Results a total of 332 overlapping differentially expressed genes (DEGs) including 73 upregulated and 259 downregulated, respectively were identified. GO analysis revealed that the DEGs were principally regulating various cancer-associated functions and pathways. The module analysis revealed 55 hub genes in 4 modules. The survival analysis through Kaplan-Meier (KM) plotter indicated that the altered expression of these genes resulted in the poor overall survival (OS) of LUCA patients. Moreover, these genes show a differential expression on both protein and mRNA level in cancer patient compared to the normal. In addition, in addition, 6 potential microRNAs (miRNAs) interacting with hub genes were identified. Finally, a list of 117 therapeutic small molecules was tabulated that could facilitate LUCA treatment. Conclusions the findings of this study may help in the development of novel and reliable biomarkers for diagnosis, prognosis and therapeutic intervention for LUAD.

scholarly journals A mRNA-miRNA-lncRNA regulatory network related to potential pathogenesis and prognostic markers of Non- small cell lung cancer

2021 ◽  
Author(s):  
Fei Wang ◽  
Chong Yuan ◽  
Yanfang Yang ◽  
Bo Liu ◽  
Hezhen Wu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Malignant Tumors ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Incidence And Mortality ◽  
Nsclc Patients

Abstract Non-small cell lung cancer (NSCLC) is one of the most malignant tumors with the fastest increasing incidence and mortality rate, but the etiology of NSCLC is still not clear. Most of lncRNAs have some structural similarities with mRNAs, suggesting that miRNAs negatively regulate the expression of lncRNAs to affect the occurrence and development of tumor. Therefore, system bioinformatics was used to explore the potential biomarkers and possible pathogenesis of NSCLC in this study. Firstly, all the clinical information and transcriptome data were downloaded from GEO and TCGA databases. R language was used to analyze the differentially expressed genes (DEGs) in NSCLC and normal lung tissues. Then, 50 overlapped DEGs were obtained via Venn database, including 10 down-regulated mRNAs and 40 down-regulated mRNAs. Secondly, the top 20 DEGs were selected for KEGG pathway and GO enrichment analysis. After screening 4 HUB genes related to the survival and prognosis of NSCLC patients, their prognosis models were established. Meanwhile, HUB genes related miRNAs and lncRNAs were screened. Finally, a mRNA-miRNA-lncRNA network related to the survival and prognosis of NSCLC patients was established, including 4 up-regulated mRNAs, 3 up-regulated miRNAs, 10 down-regulated miRNAs, 6 up-regulated lncRNAs and 19 down-regulated lncRNAs. Subject terms: Non-small cell lung cancer, mRNA-miRNA-lncRNA, pathogenesis, prognostic biomarkers.

scholarly journals Human Anergic CD4+ T Cells Can Act as Suppressor Cells by Affecting Autologous Dendritic Cell Conditioning and Survival

2002 ◽  
Vol 168 (3) ◽  
pp. 1060-1068 ◽  
Author(s):  
Loredana Frasca ◽  
Cristiano Scottà ◽  
Giovanna Lombardi ◽  
Enza Piccolella
Keyword(s):  
T Cells ◽  
Dendritic Cell ◽  
Cd4 T Cells ◽  
Suppressor Cells ◽  
Autologous Dendritic Cell

scholarly journals Downregulation of IFNG in CD4+ T Cells in Lung Cancer through Hypermethylation: A Possible Mechanism of Tumor-Induced Immunosuppression

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79064 ◽  
Author(s):  
Fang Wang ◽  
Jian Xu ◽  
Quan Zhu ◽  
Xuejun Qin ◽  
Yan Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cd4 T Cells

scholarly journals Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (35) ◽  
pp. 56233-56240 ◽  
Author(s):  
Hong Zheng ◽  
Xin Liu ◽  
Jianhong Zhang ◽  
Shawn J. Rice ◽  
Matthias Wagman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Poor Clinical Outcome

scholarly journals Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer

2018 ◽  
Vol 47 (6) ◽  
pp. 2407-2419 ◽  
Author(s):  
Hong-Min Wang ◽  
Xiao-Hong Zhang ◽  
Ming-Ming Feng ◽  
Yan-Jun Qiao ◽  
Li-Qun Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Background/Aims: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. Methods: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. Results: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. Conclusion: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.

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