Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.

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The Role of CBLL1 in the Prognosis and Immune Infiltration of Pan-Cancer

10.21203/rs.3.rs-91598/v1 ◽

2020 ◽

Author(s):

Qiang Guo ◽

Dan Li ◽

Yanmei Ji ◽

Jialong Guo

Keyword(s):

Mrna Expression ◽

Immune Cells ◽

Cox Regression ◽

Expression Level ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

The Relationship ◽

Pan Cancer ◽

Ucsc Database

Abstract ObjectiveThis study aims to explore the role of CBLL1 in pan-carcinoma and tumor immune infiltrates. MethodsDownload mRNA expression, mutation and clinical data in UCSC database, to analyze the relationship between CBLL1 expression and clinicopathological vlaue, and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between CBLL1 expression and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. ResultsThe levels of CBLL1 mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM. The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden, and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability. The expression level of CBLL1 was correlated with cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. ConclusionCBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.

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Prognostic and immunological value of LTB4R in pan-cancer

Mathematical Biosciences and Engineering ◽

10.3934/mbe.2021459 ◽

2021 ◽

Vol 18 (6) ◽

pp. 9336-9356

Author(s):

Sidan Long ◽

◽

Shuangshuang Ji ◽

Kunmin Xiao ◽

Peng Xue ◽

...

Keyword(s):

Immune Cells ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Negative Influence ◽

Leukotriene B4 ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Immune Infiltration ◽

Significant Difference ◽

Pan Cancer

<abstract> <sec><title>Background</title>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain. </sec> <sec><title>Methods</title>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies. </sec> <sec><title>Results</title>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns. </sec> <sec><title>Conclusion</title>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer. </sec> </abstract>

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Profiles of immune infiltration and its relevance to survival outcome in meningiomas

Bioscience Reports ◽

10.1042/bsr20200538 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Xiaodong Chen ◽

Fen Tian ◽

Peng Lun ◽

Yugong Feng

Keyword(s):

Immune Cells ◽

Clustering Analysis ◽

Immune Cell ◽

Cox Regression ◽

Cell Types ◽

Survival Outcome ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

Online Databases ◽

The Relationship

Abstract Tumor-infiltrating immune cells play a decisive part in prognosis and survival. Until now, previous researches have not made clear about the diversity of cell types involved in the immune response. The objective of this work was to confirm the composition of tumor-infiltrating immune cells and their correlation with prognosis in meningiomas based on a metagene approach (known as CIBERSORT) and online databases. A total of 22 tumor-infiltrating immune cells were detected to determine the relationship between the immune infiltration pattern and survival. The proportion of M2 macrophages was more abundant in 68 samples, reaching more than 36%. Univariate Cox regression analysis displayed that the proportion of dendritic cells was obviously related to prognosis. Hierarchical clustering analysis identified two clusters by the method of within sum of squares errors, which exhibited different infiltrating immune cell composition and survival. To summarize, our results indicated that proportions of tumor-infiltrating immune cells as well as cluster patterns were associated with the prognosis, which offered clinical significance for research of meningiomas.

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Immune infiltration of MMP14 in Pan-cancer and its prognostic effect on tumor

10.21203/rs.3.rs-555119/v1 ◽

2021 ◽

Author(s):

Minde Li ◽

Shaoyang Li ◽

Lin Zhou ◽

Le Yang ◽

Xiao Wu ◽

...

Keyword(s):

Dna Methylation ◽

Microsatellite Instability ◽

Mismatch Repair ◽

Immune Checkpoint ◽

Mutation Load ◽

Immune Infiltration ◽

Tumor Prognosis ◽

Checkpoint Genes ◽

The Relationship ◽

Pan Cancer

Abstract Background: Matrix metallopeptidase 14(MMPL4) is a member of the matrix metalloproteinase family, which interacts with tissue metalloproteinase inhibitors (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 on pan-cancer. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Methods: In this study, we used bioinformatics to analyze data from multiple databases, including TCGA, Oncomine and Kaplan-Meier Plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Results: MMP14 expression is highly associated with prognosis of a variety of cancers, tumor immunoinvasion, and has important effects on pan-oncologic mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes. Conclusion: MMP14 is highly correlated with tumor prognosis and immunoinvasion, and affects the occurrence and progression of many tumors. All these fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis and treatment of many tumors, and provide a new idea and direction for subsequent tumor immune research and treatment strategies.

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A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.586414 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jun Liu ◽

Shanqiang Zhang ◽

Wenjie Dai ◽

Chongwei Xie ◽

Ji-Cheng Li

Keyword(s):

Overall Survival ◽

Immune Cells ◽

Cox Regression ◽

Expression Profiles ◽

Prognostic Significance ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Cox Regression Analysis ◽

Pan Cancer

SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.

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Analysis of the Expression and Prognostic Value of MSH2 in Pan-Cancer Based on Bioinformatics

BioMed Research International ◽

10.1155/2021/9485273 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Wenli Qiu ◽

Ke Ding ◽

Lusheng Liao ◽

Yongchang Ling ◽

Xiaoqiong Luo ◽

...

Keyword(s):

T Cells ◽

Prognostic Value ◽

Cox Regression ◽

Cancer Susceptibility ◽

Prognostic Significance ◽

Housekeeping Gene ◽

Significant Negative Correlation ◽

Immune Infiltration ◽

Potential Biomarker ◽

Pan Cancer

Background. MutS homolog 2 (MSH2), with the function of identifying mismatches and participating in DNA repair, is the “housekeeping gene” in the mismatch repair (MMR) system. MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. However, the expression and prognostic significance of MSH2 have not been studied from the perspective of pan-cancer. Methods. The GTEx database was used to analyze the expression of MSH2 in normal tissues. The TCGA database was used to analyze the differential expression of MSH2 in pan-cancers. The prognostic value of MSH2 in pan-cancer was assessed using Cox regression and Kaplan-Meier analysis. Spearman correlations were used to measure the relationship between the expression level of MSH2 in pan-cancer and the level of immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Results. MSH2 is highly expressed in most type of cancers and significantly correlated with prognosis. In COAD, KIRC, LIHC, and SKCM, the expression of MSH2 was significantly positively correlated with the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils. In THCA, MSH2 expression correlated with CD8+T Cell showed a significant negative correlation. MSH2 had significantly negative correlations with stromal score and immune score in a variety of cancers and significantly correlated with TMB and MSI of a variety of tumors. Conclusions. MSH2 may play an important role in the occurrence, development, and immune infiltration of cancer. MSH2 can emerge as a potential biomarker for cancer diagnosis and prognosis.

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A potential role for metastasis-associated in colon cancer 1 (MACC1) as a pan-cancer prognostic and immunological biomarker

Mathematical Biosciences and Engineering ◽

10.3934/mbe.2021413 ◽

2021 ◽

Vol 18 (6) ◽

pp. 8331-8353

Author(s):

Ye Hu ◽

◽

Meiling Wang ◽

Kainan Wang ◽

Jiyue Gao ◽

...

Keyword(s):

Colon Cancer ◽

Cell Function ◽

Immune Checkpoints ◽

Immune Infiltration ◽

Kaplan Meier ◽

Tumor Mutational Burden ◽

Cancer Types ◽

R Programming ◽

The Relationship ◽

Pan Cancer

<abstract> <sec><title>Background</title>Metastasis-Associated in Colon Cancer 1(<italic>MACC1</italic>) is a validated biomarker for metastasis and is linked to survival. Although extensive experimental evidence indicates an association between <italic>MACC1</italic> and diverse cancers, no pan-cancer analyses have yet been performed for this marker, and the role of <italic>MACC1</italic> in immunology remains unknown. </sec> <sec><title>Material and Methods</title>In our study, we performed the analysis of <italic>MACC1</italic> expression and its influence on prognosis using multiple databases, including TIMER2, GEPIA2, Kaplan-Meier plotter. <italic>MACC1</italic> promoter methylation levels were evaluated using the UALCAN database. Based on the TCGA database, we explored the relationship between <italic>MACC1</italic> and tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints using the R programming language. We evaluated the association between <italic>MACC1</italic> and immune infiltration via TIMER and UALCAN. </sec> <sec><title>Results</title>Our results revealed that abnormal DNA methylation may be an important cause for the different expression of <italic>MACC1</italic> across cancer types. Meanwhile, we explored the potential oncogenic roles of <italic>MACC1</italic> and found significant prognostic value. <italic>MACC1</italic> may be related to T-cell function and the polarization of tumor-associated macrophages, especially in STAD and LGG. Its expression was associated with immune infiltration and was found to be closely related to immune checkpoint-associated genes, especially CD274 and SIGLEC15, indicating that <italic>MACC1</italic> may be a potential immune therapeutic target for several malignancies. Our paper reveals for the first time the relationship between <italic>MACC1</italic> and cancer immunology. </sec> <sec><title>Conclusions</title><italic>MACC1</italic> might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target. </sec> </abstract>

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Pan-Cancer Analysis of DNA Methylation Identifies Genes and Biological Functions Associated with Overall Survival

10.1101/2021.06.20.449136 ◽

2021 ◽

Author(s):

Romola Grace Cavet ◽

Peng Yue ◽

Guy Lawrence Cavet

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Cancer Biology ◽

Gene Clusters ◽

The Cancer Genome Atlas ◽

Biological Functions ◽

Cancer Types ◽

Genomic Regions ◽

The Relationship ◽

Pan Cancer

DNA methylation influences gene expression and is altered in many cancers, but the relationship between DNA methylation and cancer outcomes is not yet fully understood. If methylation of specific genes is associated with better or worse outcomes, it could implicate genes in driving cancer and suggest therapeutic strategies. To advance our understanding of DNA methylation in cancer biology, we conducted a pan-cancer analysis of the relationship between methylation and overall survival. Using data on 28 tumor types from The Cancer Genome Atlas (TCGA), we identified genes and genomic regions whose methylation was recurrently associated with survival across multiple cancer types. While global DNA methylation levels are associated with outcome in some cancers, we found that the gene-specific associations were largely independent of these global effects. Genes with recurrent associations across cancer types were enriched for certain biological functions, such as immunity and cell-cell adhesion. While these recurrently associated genes were found throughout the genome, they were enriched in certain genomic regions, which may further implicate certain gene families and gene clusters in affecting survival. By finding common features across cancer types, our results link DNA methylation to patient outcomes, identify biological mechanisms that could explain survival differences, and support the potential value of treatments that modulate the methylation of tumor DNA.

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Pan-Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5551036 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Fei Chen ◽

Yumei Fan ◽

Pengxiu Cao ◽

Bing Liu ◽

Jiajie Hou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Expression Profiles ◽

Prognostic Significance ◽

Deep Understanding ◽

Clinicopathological Parameters ◽

Cox Regression Analysis ◽

Pan Cancer

Emerging evidence revealed the significant roles of heat shock factor 1 (HSF1) in cancer initiation, development, and progression, but there is no pan-cancer analysis of HSF1. The present study first comprehensively investigated the expression profiles and prognostic significance of HSF1 and the relationship of HSF1 with clinicopathological parameters and immune cell infiltration using bioinformatic techniques. HSF1 is significantly upregulated in various common cancers, and it is associated with prognosis. Pan-cancer Cox regression analysis indicated that the high expression of HSF1 was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), and kidney renal papillary cell carcinoma (KIRP) patients. The methylation of HSF1 DNA was decreased in most cancers and negatively correlated with the HSF1 expression. Increased phosphorylation of S303, S307, and S363 in HSF1 was observed in some cancers. HSF1 remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. Our pan-cancer analysis provides a deep understanding of the functions of HSF1 in oncogenesis and metastasis in different cancers.

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Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors

Frontiers in Oncology ◽

10.3389/fonc.2021.717606 ◽

2021 ◽

Vol 11 ◽

Author(s):

Minde Li ◽

Shaoyang Li ◽

Lin Zhou ◽

Le Yang ◽

Xiao Wu ◽

...

Keyword(s):

Dna Methylation ◽

Immune Checkpoint ◽

Treatment Strategies ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Immune Infiltration ◽

Tumor Prognosis ◽

Checkpoint Genes ◽

The Relationship ◽

Pan Cancer

BackgroundMatrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes.MethodsIn this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan–Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ResultsMMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ConclusionMMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.

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