Prognostic Roles of LncRNA XIST and Its Potential Mechanisms in Human Cancers: A Pan-Cancer Analysis

Background: X-inactive specific transcript (XIST), it has been found, is abnormal expression in various neoplasms. This work aims to explore its potential molecular mechanisms and prognostic roles in types of malignancies. Methods: This research comprehensively investigated XIST transcription across cancers from Oncomine, TIMER 2.0 and GEPIA2. Correlations of XIST expression with prognosis, miRNAs, interacting protens, immune infiltrates, checkpoint markers and mutations of tumor-associated genes were also analyzed by public databases. Results: Compared to normal tissues, XIST was lower in BRCA, COAD, LUAD, lymphoma and OV in Oncomine; In TIMER 2.0, XIST was decreased in BRCA, KICH, THCA and UCEC, but increased in KIRC and PRAD; In GEPIA2, XIST was down-regulated in CESC, COAD, OV, READ, STAD, UCEC and UCS. Public databases also showed that XIST was a good indicator of prognosis in BRCA, CESC, COAD, STAD, OV and so on, but a bad one in KIRC, KIRP and so on. From starBase, we found 29 proteins interacting with XIST, and identified 4 miRNAs, including miR-103a-3p, miR-107, miR-130b-3p and miR-96-5p, which might be sponged by XIST in cancers. Furthermore, XIST was linked with immune infiltration, especially T cell CD4+, and was related to over 20 immune checkpoint markers. In addition, XIST was associated with several tumor-associated gene mutations in some cancers. Conclusion: In summary, abnormal expression of XIST influenced prognosis, miRNAs, immune cell infiltration and mutations of tumor-associated genes across cancers, especially BRCA and colorectal cancer. More efforts should be made to detect potential molecular mechanisms of XIST in the carcinogenesis.

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Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.644557 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiakang Ma ◽

Xiaoyan Lin ◽

Xueting Wang ◽

Qingqing Min ◽

Tonglian Wang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Immune Cell ◽

Tumor Hypoxia ◽

Gene Set Enrichment Analysis ◽

Cell Infiltration ◽

Immune Gene ◽

Immune Cell Infiltration ◽

Abnormal Expression ◽

Spearman Test ◽

Pan Cancer

Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Immune gene files were obtained from ImmLnc and ImmPort databases. Survival indices, including relapse-free and overall survival, were analyzed using the Kaplan–Meier and log-rank methods. The level of immune cell infiltration, degree of tumor hypoxia, and tumor cell stemness characteristics were quantified using the single-sample gene set enrichment analysis algorithm. The immune infiltration score and infiltration degree were evaluated using the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden and microsatellite instability were examined using the Spearman test. The LUAD-associated immune-related LINC00987/A2M axis was down-regulated in most cancer types, indicating poor survival and cancer progression. Immune cell infiltration was closely related to abnormal expression of the LINC00987/A2M axis, linking its expression to a possible evaluation of sensitivity to checkpoint inhibitors and response to chemotherapy. Abnormal expression of the LINC00987/A2M axis was characterized by heterogeneity in the degree of tumor hypoxia and stemness characteristics. The abnormal distribution of immune cells in LUAD was also verified through pan-cancer analysis. Comprehensive bioinformatic analysis showed that the LINC00987/A2M axis is a functional and effective tumor suppressor and biomarker for assessing the immune microenvironment and prognostic and therapeutic evaluations of LUAD.

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Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis

10.21203/rs.2.12276/v1 ◽

2019 ◽

Author(s):

Yiling Cao ◽

Weihao Tang ◽

Wanxin Tang

Keyword(s):

Gene Expression ◽

Lupus Nephritis ◽

Molecular Mechanisms ◽

Immune Cell ◽

Expression Profiles ◽

Gene Set Enrichment Analysis ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Spearman Correlation ◽

Core Genes

Abstract Objects Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN. Methods Datasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues of living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Result Five types of immune cells revealed important associations with LN, and monocytes emerged to be the prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features. Conclusion This study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.

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Follistatin-like 1 (FSTL1) is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Gastric Cancer

10.21203/rs.3.rs-60171/v1 ◽

2020 ◽

Author(s):

Li Li ◽

Shanshan Huang ◽

Yangyang Yao ◽

Jun Chen ◽

Junhe Li ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Immunity ◽

Survival Data ◽

Immune Cell ◽

Bioinformatic Analysis ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Western Blot Assay ◽

Immune Infiltration ◽

Normal Tissues

Abstract Background: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated.Method: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real‐time quantitative PCR (RT-qPCR) was using to analyzed protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates was analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA) and LinkedOmics database.Results: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and Immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC.Conclusion: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.

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Interleukin-18 Is a Prognostic Biomarker Correlated with CD8+ T Cell and Natural Killer Cell Infiltration in Skin Cutaneous Melanoma

Journal of Clinical Medicine ◽

10.3390/jcm8111993 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1993 ◽

Cited By ~ 8

Author(s):

Minchan Gil ◽

Kyung Eun Kim

Keyword(s):

Natural Killer ◽

Immune Cell ◽

Patient Survival ◽

Nk Cell ◽

Killer Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Interleukin 18 ◽

Effector Cells ◽

Normal Tissues

Interleukin-18 (IL-18) is a cytokine that enhances innate and adaptive immune responses. Although there are conflicting reports about the roles of IL-18 in melanoma progression, the clinical relevance of IL-18 expression has not been comprehensively studied. In this study, we investigated IL-18 expression and its correlation with patient survival and immune cell infiltration in melanoma using cancer gene expression data publicly available through various databases. IL18 mRNA expression was found to be significantly lower in melanoma tissues than normal tissues. Kaplan–Meier survival analysis showed that IL18 expression was positively correlated with patient survival. To investigate the possible mechanisms by which IL18 expression increased patient survival, we then assessed the correlation between IL18 expression and immune cell infiltration levels. Infiltration of various immune cells, especially CD8+ T and natural killer (NK) cells, which are cytolytic effector cells, was significantly increased by IL18 expression. Additionally, the expression levels of two cytolytic molecules including perforin and granzyme B were significantly positively correlated with IL18 expression. Collectively, this study provides the first evidence that IL18 expression has prognostic value for melanoma patient survival and is strongly correlated with CD8+ T and NK cell infiltration, suggesting the role of IL-18 as a biomarker for predicting melanoma prognosis.

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Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis

Genes ◽

10.3390/genes12091305 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1305

Author(s):

Jingwen Zou ◽

Kunpeng Du ◽

Shaohua Li ◽

Lianghe Lu ◽

Jie Mei ◽

...

Keyword(s):

Gene Expression ◽

Tumor Microenvironment ◽

Drug Sensitivity ◽

Molecular Mechanisms ◽

Immune Cell ◽

Metabolic Reprogramming ◽

Glutamine Metabolism ◽

Molecular Networks ◽

Cancer Types ◽

Pan Cancer

Background: In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer. Methods: We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including SLC1A5, SLC7A5, SLC3A2, SLC7A11, GLS, and GLS2, in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA–mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming. Results: We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity. Conclusions: The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.

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Transcriptional expression of ZICs as an independent indicator of survival in gliomas

10.21203/rs.3.rs-28764/v1 ◽

2020 ◽

Author(s):

Zhao cheng Han ◽

Jingnan Jia ◽

Yangting Lv ◽

Rongyanqi Wang ◽

Kegang Cao

Keyword(s):

Immune Cell ◽

Cox Regression ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Prognostic Significance ◽

Gene Mutations ◽

Cell Infiltration ◽

Low Grade ◽

Immune Cell Infiltration ◽

Expression Levels ◽

Ppi Networks

Abstract Background: The functional significance of the zinc-finger of the cerebellum (ZIC) gene family in gliomas remains to be elucidated. Methods: Clinical data from patients with gliomas, containing expression levels of ZIC genes, were extracted from CCLE, GEPIA2 and The Human Protein Atlas(HPA). Univariate survival analysis adjusted by Cox regression via OncoLnc was used to determine the prognostic significance of ZIC expression. We used cBioPortal to explore the correlation between gene mutations and overall survival (OS). ZIC expression was found to be related to immune cell infiltration in gliomas via TIMER analysis. GO term and KEGG pathway enrichment analyses were performed with Metascape. PPI networks were constructed using STRING. Result: The expression levels of ZIC1/2/4 in gliomas were significantly different from those in normal samples. High expression levels of ZIC1/2/5 were associated with poor OS in brain low-grade glioma (LGG) patients, while low ZIC3 expression combined with high ZIC4 expression was related to favourable OS in glioblastoma multiforme (GBM). ZIC mutations were associated with poor prognosis in LGG patients and related to favourable prognosis in GBM patients. We observed that the expression of ZICs was related to immune cell infiltration in glioma patients. ZICs were enriched in several pathways and biological processes involving arrhythmogenic right ventricular cardiomyopathy (ARVC) and tissue morphogenesis. The PPI network revealed that some coexpressed proteins of ZICs played a role in the pathogenesis of gliomas. Conclusions: Differences in the expression levels of ZIC genes could provide a significant marker for predicting prognosis in gliomas.

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KIF18B is a Prognostic Biomarker and Correlates with Immune Infiltrates in Pan-Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.559800 ◽

2021 ◽

Vol 8 ◽

Author(s):

Meng-jun Qiu ◽

Qiu-shuang Wang ◽

Qiu-ting Li ◽

Li-sheng Zhu ◽

Ya-nan Li ◽

...

Keyword(s):

Dna Methylation ◽

Immune Cell ◽

Prognostic Biomarker ◽

Tumor Mutation Burden ◽

R Language ◽

Normal Tissues ◽

Expression Difference ◽

Mutation Burden ◽

Cancer Types ◽

Pan Cancer

Background: Cancer is one of the deadliest diseases at present. Although effective screening and treatment can save lives to a certain extent, our knowledge of the disease is far from sufficient. KIF18B is a member of the kinesin-8 superfamily and plays a conserved regulatory role in the cell cycle. KIF18B reportedly functions as an oncogene in some human cancers, but the correlations between KIF18B and prognosis and immune-infiltrates in different cancers remain unclear.Methods: Data were collected from the TCGA, GTEx, CCLE, TIMER, and GSEA databases. The expression difference, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), tumor microenvironment (TME), immune cell infiltration, and gene co-expression of KIF18B were analyzed using the R language software.Results: KIF18B was widely upregulated in cancers, compared with normal tissues, and high KIF18B expression was associated with unfavorable prognoses. TMB, MSI, MMRs, and DNA methylation correlated with KIF18B dysregulation in cancers. KIF18B correlated closely with tumor immunity and interacted with different immune cells and genes in different cancer types.Conclusion: KIF18B could be used as a prognostic biomarker for determining prognosis and immune infiltration in pan-cancer.

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A Pan-cancer Analysis Reveals the Abnormal Expression and Drug Sensitivity of CSF1

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210608105357 ◽

2021 ◽

Vol 21 ◽

Author(s):

Xiaoshuo Dai ◽

Xinhuan Chen ◽

Wei Chen ◽

Yihuan Chen ◽

Jun Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Tumor Progression ◽

Drug Sensitivity ◽

Tumor Stage ◽

Response Analysis ◽

Immune Infiltration ◽

Normal Tissues ◽

Abnormal Expression ◽

Promoter Dna ◽

Pan Cancer

Background: Colony-stimulating factor-1 (CSF1) is a cytokine that is closely related to normal organ growth and development as well as tumor progression. Objective: We aimed to summarize and clarify the reasons for the abnormal expression of CSF1 in tumors and explore the role of CSF1 in tumor progression. Furthermore, drug response analysis may provide a reference for clinical medication. Methods: The expression of CSF1 was analyzed by TCGA and CCLE. Besides, cBioPortal and MethSurv databases were used to conduct mutation and DNA methylation analyses. Further, correlations between CSF1 expression and tumor stage, survival, immune infiltration, drug sensitivity and enrichment analyses were validated via UALCAN, Kaplan-Meier plotter, TIMER, CTRP and Coexperia databases. Results: CSF1 is expressed in a variety of tissues, meaningfully, it can be detected in blood. Compared with normal tissues, CSF1 expression was significantly decreased in most tumors. The missense mutation and DNA methylation of CSF1 may cause the downregulated expression. Moreover, decreased CSF1 expression was related with higher tumor stage and worse survival. Further, the promoter DNA methylation level of CSF1 was prognostically significant in most tumors. Besides, CSF1 was closely related to immune infiltration, especially macrophages. Importantly, CSF1 expression was associated with a good response to VEGFRs inhibitors, which may be due to the possible involvement of CSF1 in tumor angiogenesis and metastasis processes. Conclusion: The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.

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