scholarly journals DPYSL2 as potential diagnostic and prognostic biomarker linked to immune infiltration in lung adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang-Jie Wu ◽  
Ai-Tao Nai ◽  
Gui-Cheng He ◽  
Fei Xiao ◽  
Zhi-Min Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
List Type ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.

scholarly journals DPYSL2 is a Potential Diagnostic and Prognostic Biomarker Linked to Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Yangjie Wu ◽  
Aitao Nai ◽  
Guicheng He ◽  
Fei Xiao ◽  
Zhimin Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Markers ◽  
Gene Set ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background: Dihydropyrimidinase Like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored.Methods: Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan-Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results: In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan-Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cell, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2.Conclusions: In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target.

Transmembrane p24 Trafficking Protein 2 Regulates Inflammation Through the TLR4/NF-κB Signaling Pathway in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Longhua Feng ◽  
Pengjiang Cheng ◽  
Zhengyun Feng ◽  
Xiaoyu Zhang
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Inflammatory Factors ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
New Strategy

Abstract Background: To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo.Methods: TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results: TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays.Conclusions: TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway, and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.

scholarly journals H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival

2020 ◽  
Vol 9 (9) ◽  
pp. 2844
Author(s):  
Sayeh Saravi ◽  
Eriko Katsuta ◽  
Jeyarooban Jeyaneethi ◽  
Hasnat A. Amin ◽  
Matthias Kaspar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Biomarker ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Nucleotide Polymorphisms ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Normal Tissues

Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of H2AX expression to compare OS and perform gene set enrichment. qRT-PCR validated in-silico H2AX findings followed by immunohistochemistry on a tissue microarray. The association between single nucleotide polymorphisms in the area of H2AX; prevalence and five-year OC survival was tested in samples from the UK Biobank. Results: H2AX was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (p = 0.010). Gene Set Enrichment Analysis demonstrated gene sets involved in G2/M checkpoint, DNA repair mTORC1 signalling were enriched in the H2AX highly expressing OCs. Polymorphisms in the area around the gene were associated with both OC prevalence (rs72997349-C, p = 0.005) and worse OS (rs10790282-G, p = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. Conclusions: Our findings suggest that H2AX can be a novel prognostic biomarker for OC.

scholarly journals Increased Expression of LYNX1 in Ovarian Serous Cystadenocarcinoma Predicts Poor Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Hui Liu ◽  
Ao Wang ◽  
Yushan Ma
Keyword(s):  
Ovarian Cancer ◽  
Univariate Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Serous Cystadenocarcinoma ◽  
Kaplan Meier ◽  
Pathologic Features ◽  
The Relationship

Few studies have reported the function of LYNX1 in ovarian cancer. We retrieved LYNX1 gene expression data and clinical information of 376 patients with ovarian cancer from The Cancer Genome Atlas (TCGA) project website. Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical pathologic features and LYNX1 expression. The Kaplan–Meier method was used to draw survival curves of patients, and Cox regression was used to calculate the relationship between LYNX1 expression and survival rate or the clinicopathological characteristics of the patients. Gene set enrichment analysis (GSEA) was performed, and the correlation between LYNX1 expression and cancer immune infiltrates was investigated via single sample gene set enrichment analysis (ssGSEA). High LYNX1 expression in ovarian serous cystadenocarcinoma (OVs) was associated with tumor residual disease (RD). In Kaplan–Meier survival analysis, patients with OVs who also displayed high LYNX1 expression had decreased overall survival (OS) and disease-specific survival (DSS) than those with low LYNX1 expression. Univariate analysis also supported that patients with high LYNX1 expression had lower OS than those with low LYNX1 expression. LYNX1 expression has the potential to be a prognostic molecular marker of poor survival in OVs.

scholarly journals Identification of Seven Novel Ferroptosis-Related Long Non - Coding RNA Signatures as a Diagnostic Biomarker for Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Zhiyuan Zheng ◽  
Wei Wu ◽  
Zehang Lin ◽  
Shuhan Liu ◽  
Qiaoqian Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Background: Ferroptosis is a newly discovered type of programmed cell death that participates in the biological processes of various cancers. However, the mechanism by which ferroptosis modulates acute myeloid leukemia (AML) remains unclear. This study aimed to investigate the role of ferroptosis-related long non-coding RNAs (lncRNAs) in AML and establish a corresponding prognostic model.Methods: RNA-sequencing data and clinicopathological characteristics were obtained from The Cancer Genome Atlas database, and ferroptosis-related genes were obtained from the FerrDb database. The “limma” R package, Cox regression, and the least absolute shrinkage and selection operator were used to determine the ferroptosis-related lncRNA signature with the lowest Akaike information criteria (AIC). The risk score of ferroptosis-related lncRNAs was calculated and patients with AML were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier curve and Cox regression were used to evaluate the prognostic value of the risk score. Finally, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological functions of the ferroptosis-related lncRNAs.Results: Seven ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan-Meier and Cox regression analyses confirmed that risk scores were independent prognostic predictors of AML in both the training and validation groups (All P < 0.05). In addition, the area under the curve (AUC) analysis confirmed that the signatures had a good predictive ability for the prognosis of AML. GSEA and ssGSEA showed that the seven ferroptosis-related lncRNAs were related to glutathione metabolism and tumor immunity.Conclusions: In this study, seven novel ferroptosis-related lncRNA signatures (AP001266.2, AC133961.1, AF064858.3, AC007383.2, AC008906.1, AC026771.1, and KIF26B-AS1) were established. These signatures were shown to accurately predict the prognosis of AML, which would provide new insights into strategies for the development of new AML therapies.

scholarly journals Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingbo Sun ◽  
Jingzhan Huang ◽  
Jin Lan ◽  
Kun Zhou ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Western Blot ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Free Survival ◽  
Gene Set ◽  
Oncomine Database ◽  
Kaplan Meier

Abstract Background Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1. Conclusion CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.

HSF2 is a Promising Prognostic Biomarker and is Correlated With Immune Infiltration in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Bihui Han ◽  
Yanxiu Meng ◽  
Yumei Fan ◽  
Bing Liu ◽  
Jiajie Hou ◽  
...  
Keyword(s):  
Immune Cells ◽  
Critical Role ◽  
Enrichment Analysis ◽  
Normal Liver ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
The Relationship ◽  
Kaplan Meier Plotter

Abstract BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies and ranks as the second leading cause of cancer-related mortality worldwide. Heat shock factor 2 (HSF2) is a transcription factor that plays a critical role in development, particularly corticogenesis and spermatogenesis. However, studies on the expression and prognostic value of HSF2 and its association with tumor-infiltrating immune cells in HCC are still rare. MethodsThe TCGA, Oncomine, UALCAN, HCCDB and HPA databases were used to investigate HSF2 expression in HCC. Kaplan-Meier plotter, GEPIA and HCCDB databases were used to evaluate the association of HSF2 with the prognosis of HCC patients. Genetic alteration of HSF2 was examined by the cBioPortal database. The mechanism was investigated with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GESA), and the relationship between HSF2 expression and immune infiltration was explored through the TIMER database and CIBERSORT algorithm.Results In the present study, we found that HSF2 expression was significantly upregulated in HCC compared with normal liver tissues. High HSF2 expression was associated with poor survival in HCC patients. GO, KEGG and GESA analyses demonstrated that HSF2 was associated with various signaling pathways, including the immune response. Notably, HSF2 expression was significantly correlated with the infiltration levels of different immune cells. HSF2 expression also displayed a significant correlation with multiple immune marker sets in HCC. ConclusionsIn summary, we explored the clinical significance of HSF2 and provided a therapeutic basis for the early diagnosis, prognostic judgment, and immunotherapy of HCC.

scholarly journals Increased Expression of FN1 in Head and Neck Squamous Cell Carcinoma Predicts Poor Prognosis

2021 ◽  
Author(s):  
Hung-Sheng Shih ◽  
Li-Yu Hung ◽  
Ming-Yu Hsieh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier

Abstract Background: A few recent studies have addressed the function of FN1 (Fibronectin 1) in head and neck cancer. The clinical information from 500 HNSCC (Head and neck squamous cell carcinoma) patients with FN1 gene expression data set was published by The Cancer Genome Atlas (TCGA). The correlation between clinicopathologic characteristics and FN1 expression was analyzed by Logistic regression and Wilcoxon signed rank test. Survival function was performed employing Kaplan-Meier estimator, and the relationship between clinicopathological characteristics, prognostic outcome, and FN1 expression were examined by using Cox regression analysis. As Gene set enrichment analysis (GSEA) was performed, we investigated the correlation between FN1 expression and immune cell infiltrates with single-sample gene set enrichment analysis (ssGSEA). Results: Patients with high FN1 expression revealed a significantly decreased overall survival (OS), and disease-specific survival (DSS) than those with low FN1 expression in Kaplan-Meier survival analyses. According to the above results, univariate and multivariate analysis revealed that patients with high FN1 expression had lower OS than those with low FN1 expression.Conclusions: The findings of this research provide insights for FN1 may be potential prognostic biomarkers for diagnosis as well as therapeutic targets in HNSCC patients.

scholarly journals High expression of PIMREG predicts poor survival outcomes and is correlated with immune infiltrates in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11697
Author(s):  
Feng Jiang ◽  
Min Liang ◽  
Xiaolu Huang ◽  
Wenjing Shi ◽  
Yumin Wang
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Background PIMREG is upregulated in multiple cancer types. However, the potential role of PIMREG in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to explore its clinical significance in LUAD. Methods Using the Cancer Genome Atlas (TCGA) databases, we obtained 513 samples of LUAD and 59 normal samples from the Cancer Genome Atlas (TCGA) databases to analyze the relationship between PIMREG and LUAD. We used t and Chi-square tests to evaluate the level of expression of PIMREG and its clinical implication in LUAD. The prognostic value of PIMREG in LUAD was identified through the Kaplan–Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to screen biological pathways and analyze the correlation of the immune infiltrating level with the expression of PIMREG in LUAD. Results PIMREG was highly expressed in patients with LUAD. Specifically, the level of PIMREG gradually increased from pathological stage I to IV. Further, we validated the higher expression of PIMREG expressed in LUAD cell lines. Moreover, PIMREG had a high diagnostic value, with an -AUC of 0.955. Kaplan–Meier survival and Cox regression analyses revealed that the high expression of PIMREG was independently associated with poor clinical outcomes. In our prognostic nomogram, the expression of PIMREG implied a significant prognostic value. Gene set enrichment analysis (GSEA) identified that the high expression PIMREG phenotype was involved in the mitotic cell cycle, mRNA splicing, DNA repair, Rho GTPase signaling, TP53 transcriptional regulation, and translation pathways. Next, we also explored the correlation of PIMREG and tumor-immune interactions and found a negative correlation between PIMREG and the immune infiltrating level of T cells, macrophages, B cells, dendritic cells (DCs) , and CD8+ T cells in LUAD. Conclusions High levels of PIMREG correlated with poor prognosis and immune infiltrates in LUAD.

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