scholarly journals Integrative Analysis of MUC4 to Prognosis and Immune Infiltration in Pan-Cancer: Friend or Foe?

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao-Peng Gao ◽  
Jie-Jie Dong ◽  
Tian Xie ◽  
Xiaoqing Guan
Keyword(s):  
Genomic Alteration ◽  
Epigenetic Alterations ◽  
Immune Infiltration ◽  
Cancer Pathogenesis ◽  
Appropriate Treatment ◽  
Proliferation And Metastasis ◽  
Cancer Types ◽  
Cancer Tissues ◽  
Pan Cancer ◽  
Tumor Proliferation And Metastasis

MUC4, a transmembrane mucin, plays important roles in epithelial renewal and differentiation. Recent studies suggest that MUC4 has been implicated in pancreatic cancer pathogenesis and is expressed in various normal and cancer tissues. The underlying features of MUC4 across various cancer types may allow us to ensure appropriate treatment and patient monitoring. However, the contributions of MUC4 to pan-cancer have not been well characterized. In this study, we investigated the expression pattern and prognostic value of MUC4 across multiple databases. We further explored genomic and epigenetic alterations of MUC4, its association with proliferation and metastasis, and the correlation with immune infiltration in different cancers. Our results characterized the distinct expression profile and prognostic values of MUC4 in pan-cancer. Through examining its association with genomic alteration, tumor proliferation, and metastasis, as well as tumor infiltration, we revealed multiple function effects of MUC4. MUC4 may influence prognosis, proliferation, metastasis, and immune response in opposite directions. In conclusion, our findings suggested the necessity to more carefully evaluate MUC4 as a biomarker and therapeutic target and develop the new antibodies for cancer detection and intervention.

scholarly journals Pan-Cancer Analysis of Prognostic and Immune Infiltrates for CXCs

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4153
Author(s):  
Long Li ◽  
Wenchao Yao ◽  
Sen Yan ◽  
Xianghui Dong ◽  
Zhenyi Lv ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Intestinal Flora ◽  
Clinical Samples ◽  
Mrna Levels ◽  
Immune Infiltration ◽  
Pancreatic Cancers ◽  
Multiple Datasets ◽  
Geo Dataset ◽  
Cancer Tissues ◽  
Pan Cancer

Background: CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Methods: Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.

scholarly journals A pan-cancer analysis of prognostic genes

PeerJ ◽  
2016 ◽  
Vol 3 ◽  
pp. e1499 ◽  
Author(s):  
Jordan Anaya ◽  
Brian Reon ◽  
Wei-Min Chen ◽  
Stefan Bekiranov ◽  
Anindya Dutta
Keyword(s):  
Microarray Data ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Cancer Pathogenesis ◽  
Gene Sets ◽  
Protective Genes ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Measure Of Association ◽  
Pan Cancer

Numerous studies have identified prognostic genes in individual cancers, but a thorough pan-cancer analysis has not been performed. In addition, previous studies have mostly used microarray data instead of RNA-SEQ, and have not published comprehensive lists of associations with survival. Using recently available RNA-SEQ and clinical data from The Cancer Genome Atlas for 6,495 patients, we have investigated every annotated and expressed gene’s association with survival across 16 cancer types. The most statistically significant harmful and protective genes were not shared across cancers, but were enriched in distinct gene sets which were shared across certain groups of cancers. These groups of cancers were independently recapitulated by both unsupervised clustering of Cox coefficients (a measure of association with survival) for individual genes, and for gene programs. This analysis has revealed unappreciated commonalities among cancers which may provide insights into cancer pathogenesis and rationales for co-opting treatments between cancers.

scholarly journals Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuting He ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Wenzhi Guo
Keyword(s):  
Copy Number Variations ◽  
Regulatory Genes ◽  
The Cancer Genome Atlas ◽  
Cancer Pathogenesis ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Reversible Modification ◽  
Regulator Genes ◽  
Modified Nucleobases ◽  
Pan Cancer

Abstract Background 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. Methods Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. Results After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators.

scholarly journals CD96 Correlates With Immune Infiltration and Impacts Patient Prognosis: A Pan-Cancer Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenrui Ye ◽  
Cong Luo ◽  
Fangkun Liu ◽  
Zhixiong Liu ◽  
Fenghua Chen
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Protective Factor ◽  
Immune Checkpoints ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Cancer Types ◽  
Patient Prognosis ◽  
Pan Cancer

BackgroundImmunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.MethodsHPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.ResultsIn general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79–2.66, P < 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94–0.98, P < 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.ConclusionsCD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.

scholarly journals A Pan-Cancer Analysis of Transcriptome and Survival Reveals Prognostic Differentially Expressed LncRNAs and Predicts Novel Drugs for Glioblastoma Multiforme Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongchuan Zhao ◽  
Xiaohan Sa ◽  
Nan Ouyang ◽  
Hong Zhang ◽  
Jiao Yang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Survival Data ◽  
Drug Target ◽  
Differentially Expressed ◽  
Prognostic Biomarkers ◽  
Cancer Type ◽  
Cancer Pathogenesis ◽  
Cancer Types ◽  
Novel Drug ◽  
Pan Cancer

Numerous studies have identified various prognostic long non-coding RNAs (LncRNAs) in a specific cancer type, but a comprehensive pan-cancer analysis for prediction of LncRNAs that may serve as prognostic biomarkers is of great significance to be performed. Glioblastoma multiforme (GBM) is the most common and aggressive malignant adult primary brain tumor. There is an urgent need to identify novel therapies for GBM due to its poor prognosis and universal recurrence. Using available LncRNA expression data of 12 cancer types and survival data of 30 cancer types from online databases, we identified 48 differentially expressed LncRNAs in cancers as potential pan-cancer prognostic biomarkers. Two candidate LncRNAs were selected for validation in GBM. By the expression detection in GBM cell lines and survival analysis in GBM patients, we demonstrated the reliability of the list of pan-cancer prognostic LncRNAs obtained above. By constructing LncRNA-mRNA-drug network in GBM, we predicted novel drug-target interactions for GBM correlated LncRNA. This analysis has revealed common prognostic LncRNAs among cancers, which may provide insights into cancer pathogenesis and novel drug target in GBM.

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

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><p>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.</p> </sec> <sec><title>Material and Methods</title><p>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.</p> </sec> <sec><title>Results</title><p>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.</p> </sec> <sec><title>Conclusions</title><p><italic>MACC1</italic> might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target.</p> </sec> </abstract>

scholarly journals Characterization of Glycolysis-Associated Molecules in the Tumor Microenvironment Revealed by Pan-Cancer Tissues and Lung Cancer Single Cell Data

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1788
Author(s):  
Jinfen Wei ◽  
Kaitang Huang ◽  
Zixi Chen ◽  
Meiling Hu ◽  
Yunmeng Bai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Single Cells ◽  
Gene Expression Signature ◽  
Human Lung Cancer ◽  
Driver Genes ◽  
Molecular Features ◽  
Cancer Types ◽  
Cancer Tissues ◽  
Pan Cancer

Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. There is however still a lack of molecular characterization glycolysis and comprehensive studies related to tumor glycolysis in the pan-cancer landscape. Here, we applied a gene expression signature to quantify glycolysis in 9229 tumors across 25 cancer types and 7875 human lung cancer single cells and verified the robustness of signature using defined glycolysis samples from previous studies. We classified tumors and cells into glycolysis score-high and -low groups, demonstrated their prognostic associations, and identified genome and transcriptome molecular features associated with glycolysis activity. We observed that glycolysis score-high tumors were associated with worse prognosis across cancer types. High glycolysis tumors exhibited specific driver genes altered by copy number aberrations (CNAs) in most cancer types. Tricarboxylic acid (TCA) cycle, DNA replication, tumor proliferation and other cancer hallmarks were more active in glycolysis-high tumors. Glycolysis signature was strongly correlated with hypoxia signature in all 25 cancer tissues (r > 0.7) and cancer single cells (r > 0.8). In addition, HSPA8 and P4HA1 were screened out as the potential modulating factors to glycolysis as their expression were highly correlated with glycolysis score and glycolysis genes, which enables future efforts for therapeutic options to block the glycolysis and control tumor progression. Our study provides a comprehensive molecular-level understanding of glycolysis with a large sample data and demonstrates the hypoxia pressure, growth signals, oncogene mutation and other potential signals could activate glycolysis, thereby to regulate cell cycle, energy material synthesis, cell proliferation and cancer progression.

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

2022 ◽  
Vol 8 ◽  
Author(s):  
Fei Chen ◽  
Yumei Fan ◽  
Xiaopeng Liu ◽  
Jianhua Zhang ◽  
Yanan Shang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Immune Infiltration ◽  
Cancer Types ◽  
The Relationship ◽  
Pan Cancer

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.

scholarly journals c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Chen Feng ◽  
Xiao Ying Liu ◽  
Liu Teng ◽  
Qiang Ji ◽  
Yongyan Wu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Survival ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Cancer Pathogenesis ◽  
Yin And Yang ◽  
Alternate Mechanism ◽  
P53 Activation ◽  
Cancer Types ◽  
Pan Cancer

Abstract The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as “Yin and Yang” partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.

scholarly journals Novel Immune Infiltrating Cell Signature Based on Cell Pair Algorithm Is a Prognostic Marker in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Zhang ◽  
Zeyu Wang ◽  
Ziyu Dai ◽  
Wantao Wu ◽  
Hui Cao ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Escape ◽  
High Sensitivity ◽  
Cellular Heterogeneity ◽  
Genomic Alteration ◽  
Cell Pair ◽  
Cancer Types ◽  
Pan Cancer

Tumor-infiltrating immune cells (TIICs) have become an important source of markers for predicting the clinical outcomes of cancer patients. However, measurements of cellular heterogeneity vary due to the frequently updated reference genomes and gene annotations. In this study, we systematically collected and evaluated the infiltration pattern of 65 immune cells. We constructed the Immune Cell Pair (ICP) score based on the cell pair algorithm in 3,715 samples and across 12 independent cancer types, among which, the ICP score from six cancer types was further validated in 2,228 GEO samples. An extensive tumorigenic and immunogenomic analysis was subsequently conducted. As a result, the ICP score showed a robust reliability and efficacy in predicting the survival of patients with gliomas, in pan-cancer samples, and six independent cancer types. Notably, the ICP score was correlated with the genomic alteration features in gliomas. Moreover, the ICP score exhibited a remarkable association with multiple immunomodulators that could potentially mediate immune escape. Finally, the ICP score predicted immunotherapeutic responses with a high sensitivity, allowing a useful tool for predicting the overall survival and guiding immunotherapy for cancer patients.

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