scholarly journals WT1-AS/IGF2BP2 Axis Is a Potential Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma According to ceRNA Network Comprehensive Analysis Combined with Experiments

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 25
Author(s):  
Mingxi Jia ◽  
Yi Shi ◽  
Yang Xie ◽  
Wen Li ◽  
Jing Deng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Sequencing Data ◽  
Data Set ◽  
Normal Tissues ◽  
Polymerase Chain ◽  
Prognostic Prediction ◽  
Regulation Model ◽  
Low Expression ◽  
Competitive Endogenous Rna

Lung adenocarcinoma (LUAD) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. Here, we comprehensively analyze the characteristics of. an RNA sequencing data set of LUAD samples. In total, 395 long non-coding RNAs (lncRNAs), 89 microRNAs (miRNAs), and 872 mRNAs associated with c-Myc were identified, which were differentially expressed between tumor and normal tissues. The most relevant pathway was found to be WT1-AS–miR-200a-3p–IGF2BP2 according to the rules of competitive endogenous RNA (ceRNA) regulation. WT1-AS and IGF2BP2 expression were positively correlated and increased in LUAD samples, while miR-200a-3p had relatively low expression. The high expression of WT1-AS and IGF2BP2 was associated with poor prognosis in LUAD patients, while low expression of miR-200a-3p predicted reduced survival (p < 0.05). The analysis of the multi-gene regulation model indicated that the WT1-AS (downregulation)–miR-200a-3p (upregulation)–IGF2BP2 (downregulation) pattern significantly improved the survival of LUAD patients. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were detected in LUAD cells, and the results are consistent with the bioinformatics analysis. In summary, the WT1-AS/IGF2BP2 axis is a potential prognostic biomarker in LUAD and is expected to become an effective target for diagnosis and treatment.

scholarly journals DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Chen ◽  
Junping Ding ◽  
Wenjie Huang ◽  
Lin Sun ◽  
Jinping Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Function Analysis ◽  
Mrna Level ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Diagnostic Efficiency ◽  
Protein Levels ◽  
Normal Tissues

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.

scholarly journals DOCK2 is a Biomarker for Predicting the Prognosis of Lung Adenocarcinoma and Associated with Immune Infiltration

2021 ◽  
Author(s):  
Jie He ◽  
Tongtong Zhang ◽  
Jian Sun ◽  
Guangnan Liu
Keyword(s):  
Immune Response ◽  
Lung Adenocarcinoma ◽  
Immune Cells ◽  
Bioinformatics Analysis ◽  
Cox Regression ◽  
Clinical Sample ◽  
Clinical Samples ◽  
Data Set ◽  
Immune Infiltration ◽  
Low Expression

Abstract Background: dedicator of cytokinesis 2 is an atypical guanine exchange factor, which is particularly expressed in hematopoietic cells and modulates the activation along with the migration of immune cells by activating Ras--related C3 botulinum toxin substrate (Rac). Nevertheless, the role of DOCK2 in lung adenocarcinoma (LUAD) remains unclear.Methods: Herein, we performed bioinformatics analysis of lung adenocarcinoma data abstracted from TCGA (The Cancer Genome Altas) and GEO (Gene Expression Omnibus) data resources, and combined with web tools consisting of LinkedOmics, TIMER, and TISIDB. Finally, combined with clinical lung adenocarcinoma samples, we verified the expression of DOCK2 in tissue and its effect on the prognosis of lung adenocarcinoma.Results: In the TCGA lung adenocarcinoma data set, the expression of DOCK2 was down-regulated in tumor tissues and verified in multiple independent cohorts. In addition, the low expression of DOCK2 indicates a poor overall survival(OS) in both TCGA and other GEO data sets and in our clinical samples. COX regression data illustrated that the low expression of DOCK2 was an independent predictor for OS. Functional network analysis shows that DOCK2 participates in immune response through interleukin production, neuroinflammatory response, acquired immune response, leukocyte migration and activation of lymph node cells, and is related to multiple immune-related pathways. Besides, the expression of DOCK2 was remarkably related with many kinds of tumor infiltrating immune cells.Conclusion: combined with bioinformatics analysis and clinical sample verification, our study shows that DOCK2 can independently estimate the prognosis of lung adenocarcinoma and is related to immune infiltration. As a promising prognostic indicator and potential target of immunotherapy, the potential effect of DOCK2 on lung adenocarcinoma and its molecular mechanism are worthy of further discussion.

scholarly journals A gene-based survival score for lung adenocarcinoma by multiple transcriptional datasets analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yanlu Xiong ◽  
Jie Lei ◽  
Jinbo Zhao ◽  
Qiang Lu ◽  
Yangbo Feng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Immune Escape ◽  
Clinical Stage ◽  
Prognostic Models ◽  
Immune Checkpoints ◽  
Lasso Regression ◽  
Normal Tissues ◽  
Survival Score ◽  
Prognostic Prediction

Abstract Background Lung adenocarcinoma (LUAD) remains a crucial factor endangering human health. Gene-based clinical predictions could be of great help for cancer intervention strategies. Here, we tried to build a gene-based survival score (SS) for LUAD via analyzing multiple transcriptional datasets. Methods We first acquired differentially expressed genes between tumors and normal tissues from intersections of four LUAD datasets. Next, survival-related genes were preliminarily unscrambled by univariate Cox regression and further filtrated by LASSO regression. Then, we applied PCA to establish a comprehensive SS based on survival-related genes. Subsequently, we applied four independent LUAD datasets to evaluate prognostic prediction of SS. Moreover, we explored associations between SS and clinicopathological features. Furthermore, we assessed independent predictive value of SS by multivariate Cox analysis and then built prognostic models based on clinical stage and SS. Finally, we performed pathway enrichments analysis and investigated immune checkpoints expression underlying SS in four datasets. Results We established a 13 gene-based SS, which could precisely predict OS and PFS of LUAD. Close relations were elicited between SS and canonical malignant indictors. Furthermore, SS could serve as an independent risk factor for OS and PFS. Besides, the predictive efficacies of prognostic models were also reasonable (C-indexes: OS, 0.7; PFS, 0.7). Finally, we demonstrated enhanced cell proliferation and immune escape might account for high clinical risk of SS. Conclusions We built a 13 gene-based SS for prognostic prediction of LUAD, which exhibited wide applicability and could contribute to LUAD management.

Identification of Stage-associated MicroRNAs in Lung Adenocarcinoma Based on Microarray Data

2020 ◽  
Author(s):  
Jiarui Yu ◽  
Wei Wang ◽  
Peng Gao ◽  
Siyuan Chen ◽  
Meiyue Liu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signalling Pathway ◽  
Lung Cancers ◽  
Protein Protein Interaction ◽  
Mapk Signalling Pathway ◽  
Normal Tissues ◽  
Molecular Events ◽  
Histological Variant ◽  
Prognostic Prediction ◽  
Pathway Analyses

Abstract Background: Lung adenocarcinoma (LUAD) is the most aggressive and most frequently seen histological variant of lung cancers, comprising nearly 45% of the overall cases of lung carcinoma and its incidence has been increased significantly worldwide in the last several decades. However, there was limited available evidence with respect to the signalling pathways and miRNAs related to the LUAD.Methods: To identify the differentially-expressed miRNAs (DE-miRNAs) in different stages of LUAD, we performed a microarray on 514 LUAD and 54 normal tissues. At the mean time, the potentially targeted genes as well as the highly-enriched signaling pathways and the relevant protein–protein interaction (PPI) network were analyzed and constructed by using a series of bioinformatic methods. Moreover, the identified DE-miRNAs in different stages of the LUAD were verified by using the TCGA dataset.Results : Overall 41 down-regulated -and 82 up-regulated DE-miRNAs were identified, of which 1,716 potential targeted genes were selected. Moreover, the enriched pathways of the above genes were screened by using the GO term and KEGG pathway analyses, including the AMPK signalling pathway, FoxO signalling pathway, MAPK signalling pathway, PI3K-Akt signalling pathway and hippo signalling pathway.Conclusions: Our study could provide additional understanding of the underlying molecular events and increase the precision of prognostic prediction.

scholarly journals Overexpression of miR-519d in lung adenocarcinoma inhibits cell proliferation and invasion via the association of eIF4H

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769456 ◽  
Author(s):  
Yong Bai ◽  
Chunya Lu ◽  
Guojun Zhang ◽  
Yu Hou ◽  
Yanjie Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Cell Counting ◽  
Lung Tumorigenesis ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Polymerase Chain ◽  
Proliferation And Invasion ◽  
Inhibit Cell Proliferation

Lung cancer is one of the deadliest types of cancer worldwide due to its high mortality rate. Adenocarcinoma constitutes 20%–30% of all lung cancers. In recent years, studies on the mechanisms of lung tumorigenesis and development have in part focused on the microRNAs for their crucial role in the progress of different cancers. As for our study, we demonstrated that miR-519d was differently downregulated and eIF4H was significantly overexpressed in lung adenocarcinoma via the detection of quantitative real-time polymerase chain reaction compared with the adjacent normal tissues. Furthermore, Cell Counting Kit-8 assay, colony formation assay, xenograft tumor experiment, Ki67 immunohistochemistry assay and transwell assay were performed to explain that the upregulated miR-519d could inhibit the proliferation and invasion of A549 and H1299 cells. To further advance our understanding of the mechanisms of miR-519d, we performed the bioinformatics analysis and the luciferase report assay. The results from these procedures revealed eIF4H to be one of the targets of miR-519d. Downregulated eIF4H was analogous to the overexpressed miR-519d obtained from miR-519d agomir and si-eIF4H transfection. In summary, it can be concluded that miR-519d targets eIF4H in lung adenocarcinoma to inhibit cell proliferation and invasion. This mechanism may offer new insights into the tumorigenesis and development of lung adenocarcinoma.

scholarly journals Identifying CDKN3 Gene Expression as a Prognostic Biomarker in Lung Adenocarcinoma via Meta-analysis

2015 ◽  
Vol 14s2 ◽  
pp. CIN.S17287 ◽  
Author(s):  
Xiao Zang ◽  
Min Chen ◽  
Yunyun Zhou ◽  
Guanghua Xiao ◽  
Yang Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Survival Outcomes ◽  
Detailed Mechanism ◽  
Lung Cancer Patients ◽  
Normal Tissues

Lung cancer is among the major causes of cancer deaths, and the survival rate of lung cancer patients is extremely low. Recent studies have demonstrated that the gene CDKN3 is related to neoplasia, but in the literature severe controversy exists over whether it is involved in cancer progression or, conversely, tumor inhibition. In this study, we investigated the expression of CDKN3 and its association with prognosis in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using datasets in Lung Cancer Explorer (LCE; http://qbrc.swmed.edu/lce/ ). We found that CDKN3 was up-regulated in ADC and SCC compared to normal tissues. We also found that CDKN3 was expressed at a higher level in SCC than in ADC, which was further validated through meta-analysis (coefficient = 2.09, 95% CI = 1.50–2.67, P < 0.0001). In addition, based on meta-analysis for the prognostic value of CDKN3, we found that higher CDKN3 expression was associated with poorer survival outcomes in ADC (HR = 1.65, 95% CI = 1.39–1.96, P < 0.0001), but not in SCC (HR = 1.10, 95% CI = 0.84–1.44, P = 0.494). Our findings indicate that CDKN3 maybe a prognostic marker in ADC, though the detailed mechanism is yet to be revealed.

scholarly journals GRAP2 is a Prognostic Biomarker and Correlated with Immune Infiltration in Lung Adenocarcinoma

2022 ◽  
Author(s):  
Shimao Song ◽  
Xinzhou Deng ◽  
Jincheng Wang ◽  
Jiahui Han ◽  
Zhen Peng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Adaptor Protein ◽  
Primary Therapy ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Immunohistochemistry Staining

Abstract Background: GRAP2 is an adaptor protein involved in leukocyte-specific protein-tyrosine kinase signaling; however, the prognostic value of GRAP2 and its correlation with immune cell infiltration in lung adenocarcinoma (LUAD) remain unclear.Methods: All original data were downloaded from the TCGA database and integrated via R 3.2.2. GRAP2 expression was explored with the TCGA and TIMER databases. We evaluated the influence of GRAP2 on clinical prognosis using the Kaplan-Meier plotter, Gene Expression Omnibus (GEO) database and GEPIA database. Correlations between GRAP2 and cancer immune characteristics were analyzed via TIMER and TISIDB databases. Finally, we confirmed the expression of GRAP2 in LUAD by immunohistochemistry staining.Results: Transcription levels of GRAP2 were significantly lower in several human cancers, including LUAD, than in adjacent normal tissues. We also found that tumor tissues have lower protein expression levels of GRAP2 compared with adjacent normal tissues in LUAD by immunohistochemistry staining. The down-regulated GRAP2 was associated with poorer overall survival, pathologic stage, T stage, N stage and primary therapy outcome in LUAD. Mechanically, we identified a hub gene that included a total of 91 GRAP2 co-expressed genes, which were tightly associated with immune response in LUAD. GRAP2 expression was positively correlated with infiltrating levels of B cells, CD8+ T cells, dendritic cells, eosinophils, macrophages, mast cells, Th2 cells, Th1 cells, Th17 cells, NK cells and neutrophils. GRAP2 expression level also affected the cumulative survival time of B cells and dendritic cells. GRAP2 expression is positively correlated with multiple immune markers, chemokines, chemokine receptors and MHC molecules of LUAD.Conclusions: These findings suggest that GRAP2 is a tumor suppressor gene and can be used as a prognostic biomarker for determining prognosis and immune infiltration in LUAD.

scholarly journals OLFML2B is a Prognostic Biomarker in Lung Adenocarcinoma and Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Shuo Wang ◽  
Jun Zhang ◽  
Fanjie Meng ◽  
Yijie Yan ◽  
Bin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Squamous Cell ◽  
Prognostic Biomarker ◽  
Smoking Habit ◽  
Family Members ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Objective: The olfactomedin (OLF) and olfactomedin-like (OLFML) domain family consists of at least four members, including OLFML2B, which promotes the EMT, metastasis and invasion of cancer. However, the function of OLFML2B in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) remains unclear. The aim of this study was to clarify the clinical significance of OLFML2B in LUAD and LUSC.Methods: The genetic alteration and expression of OLFML family genes were analyzed in cBioPortal, Oncomine and TIMER database, respectively. In addition, GEPIA and UALCAN database were used to evaluate the mRNA expression of OLFML2B in LUAD and LUSC and the correlation with clinicopathological features. The protein expression of OLFML2B in STAD was explored in The Human Protein Atlas. Furthermore, the prognostic value of OLFML2B was estimated with overall survival (OS) and post-progression survival (PPS) in Kaplan-Meier plotter database. In order to evaluate the association between OLFML2B expression and cancer immune infiltrations, TIMER database was evacuated. GO enrichment and GSEA analysis were performed between OLFML2B and the associated genes associated from The Cancer Genome Atlas (TCGA) database. The single-cell RNA sequence (scRNA-seq) of OLFML family members were detected in TISCH database.Results: We found varying degrees of genetic variation among the four OLFML family members, among which OLFML2B displayed the highest incidence rate of genetic variations. The OLFML2B mRNA expression was found to be significantly higher in various cancerous tissues compared with adjacent normal tissues, including LUAD. The protein level of OLFML2B suggested the upregulation in LUAD and LUSC compared with adjacent normal tissues. The further exploration of OLFML2B in clinical indicated it correlated to the smoking habit, later clinical stages, nodal metastasis and TP53 mutation in LUAD and LUSC patients. The Kaplan-Meier analyses revealed that the increased OLFML2B level was significantly associated with the poor prognosis of LUAD patients. OLFML2B mRNA expression level had obviously negative correlations with infiltrating levels of CD8+ and CD4+ T cells, whereas was significantly associated with Treg cells, tumor-associated macrophages, neutrophils and dendritic cells. GSEA results revealed that inflammation response was significantly enriched in samples with higher expression of OLFML2B.Conclusions: These findings suggest that OLFML2B works as a prognostic biomarker for determining prognosis and immune infiltration, which is considered as a predictor of the effectiveness of immunotherapy in LUAD and LUSC. The scRNA-seq analysis revealed that OLFML2B promoted the tumor growth and aggressiveness of LUAD and LUSC.

scholarly journals Downregulation of miR-199a-3p in Hepatocellular Carcinoma and Its Relevant Molecular Mechanism via GEO, TCGA Database and In Silico Analyses

2020 ◽  
Vol 19 ◽  
pp. 153303382097967
Author(s):  
An-gui Liu ◽  
Yu-yan Pang ◽  
Gang Chen ◽  
Hua-Yu Wu ◽  
Rong-Quan He ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Data Sets ◽  
Sequencing Data ◽  
Chip Data ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Multiple Data ◽  
Multiple Data Sets ◽  
Polymerase Chain ◽  
Underlying Mechanisms

Existing reports have demonstrated that miR-199a-3p plays a role as a tumor suppressor in a variety of human cancers. This study aims to further validate the expression of miR-199a-3p in HCC and to explore its underlying mechanisms by using multiple data sets. Chip data or sequencing data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were integrated to assess the expression of miR-199a-3p in HCC. The potential targets and transcription factor regulatory network of miR-199a-3p in HCC were determined and possible biological mechanism of miR-199a-3p was analyzed with bioinformatics methods. In the results, miR-199a-3p expression was significantly lower in HCC tissues compared to normal tissues according to chip data or sequencing data and qRT-PCR. Moreover, 455 targets of miR-199a-3p were confirmed, and these genes were involved in the PI3K-Akt signaling pathway, pathways in cancer, and focal adhesions. LAMA4 was considered a key target of miR-199a-3p. In CMTCN, 11 co-regulatory pairs, 3 TF-FFLs, and 2 composite-FFLs were constructed. In conclusion, miR-199a-3p was down regulated in HCC and LAMA4 may be a potential target of miR-199a-3p in HCC.

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