scholarly journals Comprehensive Analysis Revealed that CDKN2A is a Biomarker for Immune Infiltrates in Multiple Cancers

Author(s):  
Zheng Chen ◽  
Yingjie Guo ◽  
Da Zhao ◽  
Quan Zou ◽  
Fusheng Yu ◽  
...  

The CDKN2A (cyclin dependent kinase inhibitor 2A/multiple tumor suppressor 1) gene, also known as the P16 gene, encodes multiple tumor suppressor 1 (MTS1), which belongs to the INK4 family. In tumor tissue, CDKN2A has a high expression level compared with normal tissue and reflects prognosis in tumor patients. Our research targeted the analysis of CDKN2A expression in 33 tumors and clinical parameters, patient prognosis and tumor immunity roles. The CDKN2A expression level was significantly correlated with the tumor mutation burden (TMB) in 10 tumors, and the expression of CDKN2A was also correlated with MSI (microsatellite instability) in 10 tumors. CDKN2A expression was associated with infiltrating lymphocyte (TIL) levels in 22 pancancers, thus suggesting that CDKN2A expression is associated with tumor immunity. Enrichment analysis indicated that CDKN2A expression was involved in natural killer cell-mediated cytotoxicity pathways, antigen processing and presentation, olfactory transduction pathways, and regulation of the autophagy pathway in multiple cancers. CDKN2A was significantly associated with several immune cell infiltrates in pantumors. CDKN2A may serve as a promising prognostic biomarker and is associated with immune infiltrates across cancers.

2021 ◽  
Author(s):  
Tian peng Huang ◽  
Wei Ye ◽  
Xue jiao Lin

Abstract Background Secretory phosphoprotein 1 (SPP1) is a glyco-phosphoprotein that is widely expressed in a variety of cancer cells. Current studies have identified that SPP1 is differentially expressed in a variety of cancer cell species. However, there are few studies on the level of SPP1 expression in different types of cancer and its clinical significance. Methods In this study, we analyzed SPP1 levels and its significance in 33 different cancer types by using The Cancer Genome Atlas (TCGA) database. The study analyzed the correlation between SPP1 expression and tumor immunity. Results The results showed that SPP1 transcript levels were aberrantly expressed in most tumors. Univariate Cox analysis showed that SPP1 was strongly associated with Overall survival in multiple tumor types. We also found that SPP1 was significantly correlated with tumor immune microenvironment, tumor immune cells, and tumor infiltrating lymphocyte markers. The correlation of SPP1 with Tumor mutational load (TMB) and Microsatellite instability (MSI) also predicts its role in assessing the efficacy of immunotherapy. Gene set enrichment analysis of 33 cancer types provided further evidence for the relationship between SPP1 levels and cancer progression and immune cell infiltration. Conclusion our study concludes that SPP1 plays an important role in tumorigenesis and tumor immunity and can be used as a marker for the assessment of clinical indicators in multiple cancer types.


2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.


2019 ◽  
Vol 19 (6) ◽  
pp. 772-782
Author(s):  
Shuang Zhao ◽  
Ye Zhang ◽  
Xujun Liang ◽  
Maoyu Li ◽  
Fang Peng ◽  
...  

Background:DNA methylation, which acts as an expression regulator for multiple Tumor Suppressor Genes (TSGs), is believed to play an important role in Nasopharyngeal Carcinoma (NPC) development.Methods:We compared the effects of 5-aza-2-deoxycytidine (decitabine, DAC) on gene expression using RNA sequencing in NPC cells.Results:We analyzed Differentially Expressed Genes (DEGs) in NPC cells using DAC demethylation treatment and found that 2182 genes were significantly upregulated (≥ 2-fold change), suggesting that they may play a key role in cell growth, proliferation, development, and death. For data analysis, we used the Gene Ontology database and pathway enrichment analysis of the DEGs to discover differential patterns of DNA methylation associated with changes in gene expression. Furthermore, we evaluated 74 methylated candidate TSGs from the DEGs in NPC cells and summarized these genes in several important signaling pathways frequently disrupted by promoter methylation in NPC tumorigenesis.Conclusion:Our study analyzes the DEGs and identifies a set of genes whose promoter methylation in NPC cells is reversed by DAC. These genes are potential substrates of DNMT inhibitors and may serve as tumor suppressors in NPC cells.


2021 ◽  
Author(s):  
Danxiang Chen ◽  
Cong Jin ◽  
Xubin Dong ◽  
Jialiang Wen ◽  
Erjie Xia ◽  
...  

Abstract Recently some evidences have demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of PSMB8 expression profile among 33 types of cancer in TCGA database. The results show that overexpression of PSMB8 was associated with the poor clinical outcomes in overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightfowardly in the form of immune scores, tumour-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumour mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative pCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for the prognosis determination in multiple cancers.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3484
Author(s):  
Jisun Lim ◽  
Yeon Bi Han ◽  
Soo Young Park ◽  
Soyeon Ahn ◽  
Hyojin Kim ◽  
...  

Many studies support a stepwise continuum of morphologic changes between atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma (ADC). Here we characterized gene expression patterns and the association of differentially expressed genes and immune tumor microenvironment behaviors in AAH to ADC during ADC development. Tumor tissues from nine patients with ADC and synchronous multiple ground glass nodules/lesions (GGN/Ls) were analyzed using RNA sequencing. Using clustering, we identified genes differentially and sequentially expressed in AAH and ADC compared to normal tissues. Functional enrichment analysis using gene ontology terms was performed, and the fraction of immune cell types was estimated. We identified up-regulated genes (ACSL5 and SERINC2) with a stepwise change of expression from AAH to ADC and validated those expressions by quantitative PCR and immunohistochemistry. The immune cell profiles revealed increased B cell activities and decreased natural killer cell activities in AAH and ADC. A stepwise change of differential expression during ADC development revealed potential effects on immune function in synchronous precursors and in tumor lesions in patients with lung cancer.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5667 ◽  
Author(s):  
Diangeng Li ◽  
Peng Wang ◽  
Yi Yu ◽  
Bing Huang ◽  
Xuelin Zhang ◽  
...  

Background Acetylsalicylic acid was renamed aspirin in 1899, and it has been widely used for its multiple biological actions. Because of the diversity of the cellular processes and diseases that aspirin reportedly affects and benefits, uncertainty remains regarding its mechanism in different biological systems. Methods The Drugbank and STITCH databases were used to find direct protein targets (DPTs) of aspirin. The Mentha database was used to analyze protein–protein interactions (PPIs) to find DPT-associated genes. DAVID was used for the GO and KEGG enrichment analyses. The cBio Cancer Genomics Portal database was used to mine genetic alterations and networks of aspirin-associated genes in cancer. Results Eighteen direct protein targets (DPT) and 961 DPT-associated genes were identified for aspirin. This enrichment analysis resulted in eight identified KEGG pathways that were associated with cancers. Analysis using the cBio portal indicated that aspirin might have effects on multiple tumor suppressors, such as TP53, PTEN, and RB1 and that TP53 might play a central role in aspirin-associated genes. Discussion The results not only suggest that aspirin might have anti-tumor actions against multiple cancers but could also provide new directions for further research on aspirin using a bioinformatics analysis approach.


2021 ◽  
Vol 11 ◽  
Author(s):  
Junsheng Zhao ◽  
Zhongli Yang ◽  
Mingmin Tu ◽  
Wei Meng ◽  
Hainv Gao ◽  
...  

BackgroundSolute carrier family 1 member 5 (SLC1A5) is a major glutamine transporter and plays a key role in tumor growth. The main objectives of this study were to visualize the prognostic landscape of SLC1A5 in multiple cancers and determine the relations between SLC1A5 expression and tumor immunity.MethodsSLC1A5 expression and its effect on tumor prognosis were analyzed using multiple online tools Oncomine, Gene Expression Profiling Interactive Analysis, PrognoScan, and Kaplan-Meier plotter with their own datasets as well as the data from The Cancer Genome Atlas. The correlations between SLC1A5 and tumor immune infiltrates were determined via TIMER.ResultsSLC1A5 expression was significantly higher in several types of cancers, including hepatocellular carcinoma (HCC), compared with corresponding normal tissues. High SLC1A5 expression correlated with poor overall survival and with disease-free survival related to alcohol consumption. Moreover, SLC1A5 expression correlated positively with the numbers of tumor-infiltrating B cells, CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC and in lower-grade glioma (LGG). Also, SLC1A5 expression showed strong correlations with diverse immune marker sets in HCC and LGG, indicating its role in regulating tumor immunity.ConclusionsSLC1A5 represents a useful prognostic biomarker in multiple cancers, and its expression correlates highly with tumor immune-cell infiltration, especially in HCC and LGG.


2021 ◽  
Author(s):  
Xiangyi Chen ◽  
Dechen Yu ◽  
Hai-Yu Zhou ◽  
XiaoBo Zhang ◽  
Yicun Hu ◽  
...  

Abstract Background: The primary function of the Karyophorin alpha family (KPNAs) is to assist the transport of proteins from the cytoplasm to the nucleus. Studies have found that KPNAs are involved in the occurrence and development of a variety of tumors. However, the expression level of KPNAs family members in HCC, its influence on prognosis, its relationship with immune infiltration, and its clinical significance are still unclear.Methods: We used UALCAN, GEPIA, HPA, TIMER, Kaplan-Meier Plotter, CBioPortal, String and Metascape databases to analyze the expression and mutation of KPNAs in Hepatocellular carcinoma (HCC), the expression level of KPNAs and the prognosis of patients, tumor immune cell infiltration, HCC clinicopathological characteristics Relationship. Finally, the biological functions of KPNAs related genes are analyzed. Results: The protein and mRNA of KPNAs were significantly up-regulated in HCC, and their expression levels were closely related to the prognosis of patients and the clinical characteristics of the tumor (tumor grade, stage, etc.). In addition, KPNAs in HCC are prone to mutations, which are not conducive to the prognosis of patients. Moreover, the expression of HCC is positively correlated with the infiltration of immune cells. Enrichment analysis found that KPNAs-related genes are mainly related to biological processes such as nuclear and cytoplasmic signaling, protein chromosome localization, and their pathways mainly include cell cycle and MAPK signaling pathways. Conclusion: KPNAs are significantly related to the occurrence, development and patient prognosis of HCC and may become the target of HCC immunotherapy in the future.


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