A Pan-Cancer Analysis Revealing the Role 2 of TIGIT in Tumor Microenvironment

Abstract T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression. However its role in tumor immunity and correlation with the genetic and epigenetic alterations remains unknown.Here, we comprehensively analyzed the expression patterns of the TIGIT and its value of prognostic prediction among 33 types of cancers based on the data collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects (GTEx). Furthermore, the correlations of TIGIT with tumor-infiltrating immune cells (TIICs), immune checkpoint genes, the degree of Estimation of STromal and Immune cells in MAlignant Tumor tissues using the Expression data (ESTIMATE), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) genes, and DNA methyltransferases (DNMTs) were also explored. Gene functional enrichment was conducted by Gene Set Enrichment Analysis (GSEA). Our results showed that the expression of TIGIT was upregulated in most of the cancer types. Cox regression model showed that high expression of TIGIT in tumor samples correlates with poor prognosis in KIRC, KIRP, LGG, UVM, and with favorable prognosis in BRCA, CECS , HNSC, SKCM. TIGIT expression significantly correlated with TIICs and the degree of ESTIMATE in KIRC, KIRP and UVM. TIGIT expression also correlated with CTLA4, PDCD1 (PD-1), CD274 (PD-L1), ICOS in most of the cancer types. Furthermore, the expression of TIGIT was correlated with TMB, MSI, MMR genes and DNMTs in different types of cancers. GSEA analysis showed that the expression of TIGIT was related to cytokine-cytokine receptor interaction, allograft rejection, oxidative phosphorylation.These findings suggested that TIGIT could serve as a potential biomarker for prognosis and a novel target for immunotherapies in cancers.

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A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

Scientific Reports ◽

10.1038/s41598-021-01933-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jie Wen ◽

Xueyi Mao ◽

Quan Cheng ◽

Zhixiong Liu ◽

Fangkun Liu

Keyword(s):

T Cells ◽

Immune Cells ◽

Immune Checkpoint ◽

Expression Patterns ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction ◽

Mmr Genes ◽

Potential Biomarker ◽

Cancer Types

AbstractT cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression. However its role in tumor immunity and correlation with the genetic and epigenetic alterations remains unknown. Here, we comprehensively analyzed the expression patterns of the TIGIT and its value of prognostic prediction among 33 types of cancers based on the data collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects (GTEx). Furthermore, the correlations of TIGIT with pathological stages, tumor-infiltrating immune cells (TIICs), signatures of T cells subtypes, immune checkpoint genes, the degree of Estimation of STromal and Immune cells in MAlignant Tumor tissues using the Expression data (ESTIMATE), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) genes, and DNA methyltransferases (DNMTs) were also explored. Gene functional enrichment was conducted by Gene Set Enrichment Analysis (GSEA). Our results showed that the expression of TIGIT was upregulated in most of the cancer types. Cox regression model showed that high expression of TIGIT in tumor samples correlates with poor prognosis in KIRC, KIRP, LGG, UVM, and with favorable prognosis in BRCA, CECS, HNSC, SKCM. TIGIT expression positively correlated with advanced stages, TIICs, the signatures of effector T cells, exhausted T cells, effector Tregs and the degree of ESTIMATE in KIRC, KIRP and UVM. TIGIT expression also positively correlated with CTLA4, PDCD1 (PD-1), CD274 (PD-L1), ICOS in most of the cancer types. Furthermore, the expression of TIGIT was correlated with TMB, MSI, MMR genes and DNMTs in different types of cancers. GSEA analysis showed that the expression of TIGIT was related to cytokine-cytokine receptor interaction, allograft rejection, oxidative phosphorylation. These findings suggested that TIGIT could serve as a potential biomarker for prognosis and a novel target for immunotherapies in cancers.

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Integrated Analysis of FAM57A Expression and Its Potential Roles in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.719973 ◽

2021 ◽

Vol 11 ◽

Author(s):

Junwei Wei ◽

Yun Liu ◽

Caiyan Zhao

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Integrated Analysis ◽

Functional Assay ◽

Lung Carcinogenesis ◽

Checkpoint Genes

BackgroundFamily with sequence similarity 57 member A (FAM57A) is a membrane associated gene contributing to lung carcinogenesis. In hepatocellular carcinoma (HCC) and other cancers, whether FAM57A exerts similar roles has been rarely reported. Herein, the biological functions and clinical significance of FAM57A in HCC were explored.MethodsInitially the differential expression of FAM57A between nontumor and HCC tissues was validated using a number of publicly accessible databases and immunohistochemistry (IHC). Then, the Kruskal–Wallis rank sum test or the Wilcoxon rank sum test as well as logistic regression were employed to analyze the association of FAM57A expression with clinical characteristics of HCC. The Cox regression and Kaplan–Meier analyses were conducted to assess the prognostic significance. Besides, with the coexpression analysis, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the molecular pathomechanisms that were mediated by FAM57A in HCC were elucidated. Furthermore, the correlations between FAM57A expression and tumor-infiltrating immune cells (TIICs) or immune checkpoint genes were analyzed. Finally, in vitro cell functional assay was carried out to preliminarily verify the role of FAM57A in HCC.ResultsFAM57A expression was demonstrated to be higher in HCC samples than in nontumor samples (all p-values <0.05), statistically correlated with clinicopathological characteristics (clinical stage, T stage, pathological grade), and inversely correlated to HCC patient survival. Univariate and multivariate Cox regression analyses showed that FAM57A expression could independently predict prognosis in HCC patients. Functional enrichment analyses further indicated that FAM57A was involved in multiple tumor-related pathways. FAM57A expression was positively correlated with TIICs, gene markers of TIICs, as well as immune checkpoint genes. Also, high expression of FAM57A predicted a poor prognosis for HCC based on immune cell subgroups. Functional assay of FAM57A knockdown significantly inhibited cell proliferation and induced cell apoptosis in HCC cells.ConclusionsOur results indicated that FAM57A could be used as a biomarker to predict the prognosis and immunotherapy response for HCC patients and might function as an oncogene to promote HCC progression.

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Pan-Cancer Analysis Revealed SRSF9 as a New Biomarker for Prognosis and Immunotherapy

Journal of Oncology ◽

10.1155/2022/3477148 ◽

2022 ◽

Vol 2022 ◽

pp. 1-21

Author(s):

Jinhui Liu ◽

Yuanyuan Wang ◽

Jian Yin ◽

Yan Yang ◽

Rui Geng ◽

...

Keyword(s):

Cancer Patients ◽

Immune Checkpoint ◽

Negative Relationship ◽

Dna Methyltransferases ◽

Gene Set Enrichment Analysis ◽

Mmr Genes ◽

Free Interval ◽

Cancer Types ◽

Immune Score ◽

Pan Cancer

Background. Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. However, whether SRSF9 has a crucial role across pan-cancer is still unknown. Methods. In this study, we used public databases, such as The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx), to analyze SRSF9 expression level among tumor and normal cells. Survival analysis, K-M plotter, and PrognoScan were used to analyze the prognosis value of SRSF9, regarding to overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Moreover, we performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. Results. In general, SRSF9 expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which SRSF9 was associated with short survival and severe progression. In COAD, STAD, and UCEC, SRSF9 expression was positively related to both TMB and MSI. In BRCA, BLCA, ESCA, GBM, HNSC, LUSC, LUAD, OV, PRAD, TGCT, THCA, and UCEC, both immune score and stomal score showed a negative relationship with SRSF9 expression. Immune score showed a positive relationship with SRSF9 expression in LGG. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In LIHC, SRSF9 was highly significant correlated with most immune checkpoint genes. For neoantigens, correlation between SRSF9 and the quantity of neoantigens was significantly positive in some cancer types. SRSF9 was also correlated with MMR genes, m6A genes, and DNA methyltransferases. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. Conclusion. These findings demonstrated that SRSF9 may be a new biomarker for the prognosis and immunotherapy in various cancers. As a result, it will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients.

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Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma

BMC Cancer ◽

10.1186/s12885-021-07788-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rui Zhang ◽

Qi Li ◽

Jialu Fu ◽

Zhechuan Jin ◽

Jingbo Su ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Cox Regression ◽

Tnm Stage ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Tumor Mutation Burden ◽

Kaplan Meier ◽

Mutation Burden ◽

Significant Difference ◽

Genomic Mutation

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients. Methods Whole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan–Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients. Results The mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan–Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA. Conclusions Mutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.

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APLN: A potential novel biomarker for cervical cancer

Science Progress ◽

10.1177/00368504211011341 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110113

Author(s):

Yusha Chen ◽

Xiaoqian Lin ◽

Jinwen Zheng ◽

Jiancui Chen ◽

Huifeng Xue ◽

...

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Clinical Stage ◽

Mapk Signaling ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Receptor Interaction ◽

Primary Therapy ◽

Advanced Clinical Stage

Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21–3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03–4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03–2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.

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NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma

10.21203/rs.3.rs-880002/v1 ◽

2021 ◽

Author(s):

Chenxi Yuan ◽

Qingwei Wang ◽

Xueting Dai ◽

Yipeng Song ◽

Jinming Yu

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Immune Cells ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

The Impact ◽

Nlrp3 Expression

Abstract Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.

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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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Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽

10.7717/peerj.8348 ◽

2020 ◽

Vol 8 ◽

pp. e8348

Author(s):

Mei Chen ◽

Shufang Zhang ◽

Xiaohong Wen ◽

Hui Cao ◽

Yuanhui Gao

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Multivariate Analyses ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Receptor Interaction ◽

Normal Tissues

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.

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Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

10.21203/rs.3.rs-1232206/v1 ◽

2022 ◽

Author(s):

Yang Bu ◽

Kejun Liu ◽

Yiming Niu ◽

Ji Hao ◽

Lei Cui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Liver Cancer ◽

Immune Cell ◽

Cox Regression ◽

Functional Enrichment ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Potential Biomarker ◽

Glucose 6 Phosphate Dehydrogenase

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

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The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽

10.3390/biom9090429 ◽

2019 ◽

Vol 9 (9) ◽

pp. 429 ◽

Cited By ~ 24

Author(s):

Zou ◽

Zheng ◽

Deng ◽

Yang ◽

Xie ◽

...

Keyword(s):

Tumor Microenvironment ◽

Signaling Pathway ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

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