scholarly journals The Oncogenic Role and Immune Infiltration for CARM1 Identified by Pancancer Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kui Liu ◽  
Jing Ma ◽  
Jiao Ao ◽  
Lili Mu ◽  
Yixian Wang ◽  
...  

Chromatin-modifying enzymes, especially protein arginine methyltransferases (PRMTs), have been identified as candidate targets for cancer. Cellular or animal-based evidence has suggested an association between coactivator-linked arginine methyltransferase 1 (CARM1) and cancer progression. However, the relationship between CARM1 and patient prognosis and immune infiltration in pancancer patients is unknown. On the basis of the GEO and TCGA databases, we first investigated the possible oncogenic functions of CARM1 in thirty-three tumor types. CARM1 expression was elevated in many types of tumors. In addition, there was a significant association between CARM1 expression and the survival rate of tumor patients. Uterine corpus endometrial carcinoma (UCES) samples had the highest CARM1 mutation frequency of all cancer types. In head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), CARM1 expression was associated with the level of CD8+ T cell infiltration, and cancer-associated fibroblast infiltration was also observed in other tumors including kidney renal papillary cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). CARM1 was involved in immune modulation and played an important role in the tumor microenvironment (TME). Furthermore, activities associated with RNA transport and its metabolism were included in the possible mechanisms of CARM1. Herein, our first pancancer research explores the oncogenic role of CARM1 in various tumors. CARM1 is associated with immune infiltrates and can be employed as a predictive biomarker in pancancer.

2021 ◽  
Vol 11 ◽  
Author(s):  
Chang Gu ◽  
Jiafei Chen ◽  
Xuening Dang ◽  
Chunji Chen ◽  
Zhenyu Huang ◽  
...  

BackgroundWe investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods.MethodsThe mutational data, transcriptome data and corresponding clinical medical information of LUSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were explored. Survival analysis for the hippo core genes and the prognostic model were performed. Immune infiltration was estimated by CIBERSORT algorithm and some immune checkpoints-related genes were further investigated.ResultsOverall, 551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively. There were 1910 up-regulated DEGs and 2253 down-regulated DEGs were finally identified. The top five mutational hippo pathway core genes were LATS1 (4%), WWC1 (2%), TAOK1 (2%), TAOK3 (2%), and TAOK2 (2%), respectively. the mutation of LATS2 was highly associated with co-mutational NF2 (P <0.05) and TAOK1 (P <0.05). In survival analyses, we found only WWC1 (log-rank p = 0.046, HR = 1.32, 95% CI = 1–1.73) and LATS2 (log-rank p = 0.013, HR = 1.41, 95%CI = 1.08–1.86) had significant prognostic roles. After getting the three subgroups according to the subtyping results, we demonstrated that T cell gamma delta (p = 5.78e-6), B cell memory (p = 4.61e-4) and T cell CD4+ memory resting (p = 2.65e-5) had significant differences among the three groups. SIGLEC15 (P <0.01) and CD274 (P <0.05) also had statistical differences among the three subgroups.ConclusionsOur study verified the prognostic roles of WWC1 and LATS2 in LUSC patients. Immune checkpoints-related genes SIGLEC15 and CD274 had statistical differences among the three subgroups, which may provide new perceptions on the molecular mechanisms in LUSC and maybe helpful for precisely selecting specific LUSC patients with potential immunotherapy benefits.


Author(s):  
Min Tang ◽  
Yukun Li ◽  
Xianyu Luo ◽  
Jiao Xiao ◽  
Juan Wang ◽  
...  

Lung squamous cell carcinoma (LSCC) is one of the most common types of lung cancer in adults worldwide. With the development of modern medicine, cancer treatment that harnesses the power of the immune system might be particularly effective for treating LSCC. In this research, LSCC expression data, which quantify the cellular composition of immune cells, were analyzed by weighted gene coexpression network analysis (WGCNA) and a deconvolution algorithm based on the Gene Expression Omnibus (GEO) database, and the results indicated a close relationship between LSCC and CD8+ T cells. Six hub genes (SYT3, METTL8, HSPB3, GFM1, ERLIN2, and CLCN2) were verified by gene–gene network and protein–protein interaction (PPI) network analyses. We found that the six hub genes were increased in cancer tissues and were closely correlated with cancer development and progression. After immune correlation analysis, METTL8 was selected as a prognostic biomarker. Finally, we found that the METTL8 levels were increased in multiple lung cancer cell lines and LSCC tissues. METTL8 inhibition could clearly induce G1 cell cycle arrest and suppress proliferation. Therefore, METTL8, which is related to CD8+ T cell infiltration, might be identified as a potential biomarker and gene therapy target in LSCC.


2019 ◽  
Author(s):  
zenghong wu ◽  
xun niu ◽  
Xi-Yue Xiao ◽  
xiong chen

Abstract Objection: Head and neck squamous cell carcinoma (HNSCC), a basic malignant tumor of the head and neck distinct. As a famous heterogeneous disease, the jobs of immune cells inside the tumor-related as yet missing for HNSCC, particularly in current immunotherapy. Method: We explored the TME, TMB and evaluate the 22 TIICs subsets of immune response based on GEO and TCGA database of HNSCC to explore its relationship with atomic subpopulation, survival, function and expression difference and reveal potential targets and biomarkers for immunotherapy. Results: Observing the download of GSE6631 database contained 22 HNSCC samples and 22 normal samples and TCGA database contained 111 HNSCC and 12 normal tissues. The results suggested that the expression of macrophages M0 and T cells CD4 memory resting was significant difference and may plays an important role in regulate cancer progression (P<0.05). The result of tumor mutational burden revealed that the most common somatic mutations variant classification was missense mutation, the most common DNA sequence polymorphism type was SNP, the most common single nucleotide variants (SNV) class was C>T, the variants per sample median was 78 in HNSCC patients. Top 10 mutated genes that related to TMB was TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1 and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB and genomic alterations was additionally set up. Our paintings advance the information of immune response and offers significant assets for research to enhance immunotherapy.


2020 ◽  
Author(s):  
Zenghong Wu ◽  
Xun Niu ◽  
Xi-Yue Xiao ◽  
Xiong Chen

Abstract Background : Head and neck squamous cell carcinoma (HNSCC), a basic malignant tumor of the head and neck distinct. As a famous heterogeneous disease, the jobs of immune cells inside the tumor-related as yet missing for HNSCC, particularly in current immunotherapy. Method: We explored the TME, TMB and evaluate the 22 TIICs subsets of immune response based on GEO and TCGA database of HNSCC to explore its relationship with atomic subpopulation, survival, function and expression difference and reveal potential targets and biomarkers for immunotherapy. Results: Observing the download of GSE6631 database contained 22 HNSCC samples and 22 normal samples and TCGA database contained 111 HNSCC and 12 normal tissues. The results suggested that the expression of macrophages M0 and T cells CD4 memory resting was significant difference and may plays an important role in regulate cancer progression ( P <0.05). The result of tumor mutational burden revealed that the most common somatic mutations variant classification was missense mutation, the most common DNA sequence polymorphism type was SNP, the most common single nucleotide variants (SNV) class was C>T, the variants per sample median was 78 in HNSCC patients. Top 10 mutated genes that related to TMB was TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1 and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB and genomic alterations was additionally set up. Our paintings advance the information of immune response and offers significant assets for research to enhance immunotherapy.


2017 ◽  
Vol 24 (13) ◽  
pp. 4017-4024 ◽  
Author(s):  
Pinjie Bao ◽  
Takehiko Yokobori ◽  
Bolag Altan ◽  
Misaki Iijima ◽  
Youko Azuma ◽  
...  

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiangwei Hu ◽  
Xinqin Xiang ◽  
Wei Guan ◽  
Weihua Lou ◽  
Junming He ◽  
...  

Abstract Background So far, few have concerned miR-497-5p in lung squamous cell carcinoma (LUSC). Methods MiR-497-5p expression in LUSC was measured by qRT-PCR. Its impacts on tumor-related cell behaviors were investigated by CCK8 assay, scratch healing assay, flow cytometry and Transwell invasion methods. In addition, interaction between miR-497-5p and CDCA4 in LUSC was also elucidated through rescue experiment, western blot, dual-luciferase, and bioinformatics analysis. Results Low level of miR-497-5p was confirmed in LUSC tissue and cells. Overexpressed miR-497-5p markedly inhibited cancer progression. miR-497-5p restrained CDCA4 expression. Rescue assay showed that overexpressing miR-497-5p eliminated effect of overexpressed CDCA4. Conclusion By targeting CDCA4, miR-497-5p restrained development of LUSC.


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