Dataset Information

Systematic pan-cancer landscape identifies CARM1 as a potential prognostic and immunological biomarker.

ABSTRACT:

Background

Belonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy.

Results

Based on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis.

Conclusions

Our first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.

SUBMITTER: Qiu Y

PROVIDER: S-EPMC8761291 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although increasing evidence supports a vital role for TREM2 in tumorigenesis of some cancers, no systematic pan-cancer analysis of TREM2 is available. Thus, we aimed to explore the prognostic value, and investigate the potential immunological functions, of TREM2 across 33 cancer types. Based on datasets from The Cancer Genome Atlas, and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and Human Protein Atlas, we employed an array of bioinformatics methods to explore the potential oncogenic roles of TREM2, including analyzing the relationship between TREM2 and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration of different tumors. The results show that TREM2 is highly expressed in most cancers, but present at low levels in lung cancer. Further, TREM2 is positively or negatively associated with prognosis in different cancers. Additionally, TREM2 expression was associated with TMB and MSI in 12 cancer types, while in 20 types of cancer, there was a correlation between TREM2 expression and DNA methylation. Six tumors, including breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, were screened out for further study, which demonstrated that TREM2 gene expression was negatively correlated with infiltration levels of most immune cells, but positively correlated with infiltration levels of M1 and M2 macrophages. Moreover, correlation with TREM2 expression differed according to T cell subtype. Our study reveals that TREM2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes novel coronavirus disease 2019 (COVID-19), which is characterized by pneumonia, cytokine storms, and lymphopenia. Due to immunosuppression, cancer patients may be more susceptible to SARS-CoV-2 and have more serious complications. According to recent research, cyclic GMP-AMP synthase (cGAS) could be a potential SARS-CoV-2 sensor. However, at present, no studies have been conducted on cGAS gene alterations in pan-cancer. This study aimed to discover therapeutic implications for COVID-19-infected tumor patients by performing a comprehensive analysis of cGAS in malignant tumors.MethodscGAS expression matrices were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases, which were used to evaluate cGAS expression in various tumors, its prognostic value, and its relationship to the immune microenvironment, microsatellite instability (MSI), immune neoantigens, gene mutations, immune checkpoints, MSI, tumor mutational burden (TMB), mismatch repair (MMR) genes, and DNA methyltransferases (DNMT). We also used the cBioPortal, Human Protein Atlas (HPA), and GeneMANIA databases to explore the types of changes, gene networks and immunofluorescence localization, and protein expression of these genes.ResultsCompared to normal tissues, cGAS was highly expressed in 13 types of cancer (e.g., lung cancer) and lowly expressed in other cancers (e.g., pancreatic cancer). cGAS expression was associated with prognosis in nine cancers, such as renal clear cell carcinoma (P<0.05). Furthermore, deep deletion was the most common type of cGAS genomic mutation. DNMT, immune infiltration levels, TMB, MSI, MMR genes, neoantigens, and immune checkpoints were all correlated with cGAS expression. Moreover, we used the GSE30589 dataset to investigate the post-SARS-CoV infection changes in cGAS expression in vitro. Finally, mithramycin, MI219, AFP464, aminoflavone, kahalide F, AT13387, doxorubicin, and other drugs increased the sensitivity of cGAS expression. According to the evidence presented above, cGAS may become an important target for cancer therapy.ConclusionsThis study discovered that SARS-CoV-2-infected cancer patients might experience changes in their tumor environment as a result of cGAS, making patients with tumors expressing high cGAS more susceptible to COVID-19 and possibly a worsening prognosis. Furthermore, cGAS may be a novel biomarker for diagnosing and treating COVID-19-infected tumor patients.