Increased Expression of LYNX1 in Ovarian Serous Cystadenocarcinoma Predicts Poor Prognosis

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.

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

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02379-z ◽

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.

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

Journal of Clinical Medicine ◽

10.3390/jcm9092844 ◽

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.

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

10.21203/rs.3.rs-502041/v1 ◽

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.

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CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family

10.21203/rs.3.rs-40048/v1 ◽

2020 ◽

Author(s):

Peipei Gao ◽

Ting Peng ◽

Canhui Cao ◽

Shitong Lin ◽

Ping Wu ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Tumor Microenvironment ◽

Immune Cells ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Markers ◽

Immune Infiltration ◽

Kaplan Meier ◽

The Relationship

Abstract Background: Claudin family is a group of membrane proteins related to tight junction. There are many studies about them in cancer, but few studies pay attention to the relationship between them and the tumor microenvironment. In our research, we mainly focused on the genes related to the prognosis of ovarian cancer, and explored the relationship between them and the tumor microenvironment of ovarian cancer.Methods: The cBioProtal provided the genetic variation pattern of claudin gene family in ovarian cancer. The ONCOMINE database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to exploring the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via Kaplan-Meier plotter. Immunologic signatures were enriched by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor microenvironment of ovarian cancer were investigated via Tumor Immune Estimation Resource (TIMER).Results: In our research, claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, we found that CLDN3, CLDN4, CLDN6, CLDN10, CLDN15 and CLDN16 were significantly correlated with overall survival of patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunologic signatures about B cell, CD4 T cell and CD8 T cell. What makes more sense is that CLDN6 and CLDN10 were found related to the tumor microenvironment. CLDN6 expression was negatively correlated with immune infiltration level in ovarian cancer, and CLDN10 expression was positively correlated with immune infiltration level in ovarian cancer. Further study revealed the CLDN6 expression level was negatively correlated with gene markers of various immune cells in ovarian cancer. And, the expression of CLDN10 was positive correlated with gene markers of immune cells in ovarian cancer.Conclusions: CLDN6 and CLDN10 were prognostic biomarkers, and correlated with immune infiltration in ovarian cancer. Our results revealed new roles for CLDN6 and CLDN10, and they were potential therapeutic targets in the treatment of ovarian cancer.

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Expression Profiles and Prognostic Values of BOLA Family members in Ovarian Cancer

10.21203/rs.3.rs-95044/v1 ◽

2020 ◽

Author(s):

Mingyang Zhu ◽

Shiqi Xiao

Keyword(s):

Ovarian Cancer ◽

Metal Ion ◽

Expression Profiles ◽

Family Members ◽

Enrichment Analysis ◽

Genetic Alterations ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Gene Set ◽

Protein Disulfide Oxidoreductase

Abstract Background: The BOLA gene family, comprising 3 members, is mainly involved in the regulation of intracellular iron homeostasis. Emerging evidence suggests that BOLA family member 2 play vital roles in tumorigenesis and progression of hepatic cellular carcinoma. However, little known about its roles in ovarian cancer. Methods: In present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BOLA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein–protein interaction networks of BOLA proteins and their interactors by using String database and Cytoscape software. In addition, we performed the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying the involvement of BOLA family members in OC by using gene set enrichment analysis. Results: The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than that in normal ovarian tissues. Dysregulated mRNA expressions of three BOLA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BOLA family members in ovarian cancer. Network analysis and enrichment analysis indicated that three BOLA family members and their 20 interactors were mainly associated with metal-ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BOLA family members were mainly associated with oxidative phosphorylation, proteasome, protein export and glutathione metabolism in ovarian cancer. Conclusions: In brief, the present comprehensive bioinformatics analysis revealed that BOLA1, 2, and 3 may be new prognostic biomarkers, and BOLA2 and BOLA3 may be a potential therapeutic target of precision therapy for patients with ovarian cancer, but further studies are demanded to certify this notion.

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

Cancer Cell International ◽

10.1186/s12935-019-0986-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 17

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.

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Expression profiles and prognostic values of BolA family members in ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-021-00821-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Mingyang Zhu ◽

Shiqi Xiao

Keyword(s):

Ovarian Cancer ◽

Metal Ion ◽

Expression Profiles ◽

Family Members ◽

Enrichment Analysis ◽

Genetic Alterations ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Gene Set ◽

Protein Disulfide Oxidoreductase

Abstract Background The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer. Methods In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members’ involvement in OC by using gene set enrichment analysis. Results The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer. Conclusion In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.

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

10.21203/rs.3.rs-89953/v1 ◽

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.

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

10.21203/rs.3.rs-1033849/v1 ◽

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.

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

PeerJ ◽

10.7717/peerj.11697 ◽

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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