scholarly journals CMET-30. COMPREHENSIVE METHYLOME ANALYSIS OF EGFR-MUTANT PRIMARY LUNG ADENOCARCINOMA AND MATCHED BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Yasin Mamatjan ◽  
Michael Cabanero ◽  
Jeffrey Zuccato ◽  
Jessica Weiss ◽  
Shirin Karimi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Methylation Status ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Promoter Regions ◽  
Primary Lung Adenocarcinoma ◽  
Egfr Mutant

Abstract Brain metastasis (BM) in patients with EGFR-mutant lung adenocarcinoma is a major determinant of overall survival. Novel insight into the genetic and epigenetic underpinnings of BM development is lacking. The aim of this study is to compare the methylome of EGFR-mutant primary lung adenocarcinoma (EGFRM-PLA) and matched BM to identify important alterations for the mechanisms of BM. Matched EGFRM-PLA and BM tumors from seven patients were profiled using the Illumina Infinium MethylationEPIC BeadChip array. Unsupervised clustering analyses of the 14 samples showed a similar whole DNA methylation signatures between EGFRM-PLA and BM tumors. Furthermore, PCA plot highlighted that seven matched BM and lung tumor samples were clustered together closely based on matching pairs for the most variable probes (2.5K to 10K). These observations indicate high level of concordance and the same cell of origin. However, these fourteen samples clustered into two groups based on tumor site being lung or brain based on 83K differentially methylated CpG sites. Of the 83K probes, 2.4K were either hypermethylated or hypomethylated in all lung samples. A quarter of these 2.4K probes were located in promoter regions. Specifically, we identified differences in methylation status of EGFR/ALK promoter regions in lung tumors versus BM. CNV analyses showed higher deep deletions of chromosomes and genes in BM compared to EGFRM-PLA. Leukocytes unmethylation for purity (LUMP) scores which indicate immune cell infiltration were similar between lung and BM pairs (Mean LUMP_score=0.64) consistent with high immune cell infiltration. Our results indicated a similar whole DNA methylation signature of EGFRM-PLA and matched BM, while comprehensive analysis identified important differentially methylated probes. Distinct differences in CNV alterations were observed in lung versus brain samples. The BM and EGFRM-PLA showed similar tumor purity and immune cell components. Overall, tumor methylation profiling provides clinically important information regarding biology of BM in EGFRM-PLA.

scholarly journals Peripheral Blood-Based DNA Methylation of Long Non-Coding RNA H19 and Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promoters are Potential Non-Invasive Biomarkers for Gastric Cancer Detection

2021 ◽  
Vol 28 ◽  
pp. 107327482110436
Author(s):  
Dingtao Hu ◽  
Xiaoqi Lou ◽  
Nana Meng ◽  
Zhen Li ◽  
Ying Teng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Female Group ◽  
Immune Cell Infiltration ◽  
Non Invasive ◽  
Online Databases

Introduction The early diagnosis and detection could greatly improve the clinical outcome of gastric cancer (GC) patients. However, the non-invasive biomarkers for GC detection remain to be identified. Method We used online databases (GEPIA, UALCAN, Kaplan-Meier plotter, TIMER, and MEXPRESS) to explore the association between H19 or metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in tissues and the occurrence, development, prognosis, the levels of immune cell infiltration, and methylation of GC; the correlation between mRNA expression and DNA methylation levels of genes were also examined. Methylation levels of H19 or MALAT1 in peripheral blood were compared between 150 GC patients and 100 healthy controls (HCs). Predictive nomograms were constructed among female and male groups for GC diagnosis. The calibration curves, Hosmer–Lemeshow test, and decision curve analysis were also used to examine the nomograms’ predictive ability and clinical values. Results Using multiple online databases, we found that the mRNA expressions of H19 and MALAT1 in tissues were related to the occurrence of GC, and such expressions were associated with immune cell infiltration of GC and negatively correlated with DNA methylation levels of H19 and MALAT1. H19 gene, H19C island, and MALAT1B island, as well as 20 CpG sites were hypermethylated in peripheral blood of GC patients compared with HCs; similar results were also found in female and male groups ( P < .05 for all). The combination of H19c3, H19c4, MALAT1b12, and age, as well as the combination of H19b7, H19c1, H19c5, and age in the nomograms could distinguish GC patients from HCs in the female group and male group, respectively. Conclusion We found statistically significant hypermethylation of H19 and MALAT1 promoters in GC patients, and meaningful sensitivity and specificity of MALAT1 and H19 methylation in discriminating GC and HCs were observed in both female and male groups, which indicates that the peripheral blood-based DNA methylation of H19 and MALAT1 could act as potential non-invasive biomarkers for the diagnosis of GC.

scholarly journals SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

2021 ◽  
Author(s):  
Lu Yuan ◽  
Xixi Wu ◽  
Longshan Zhang ◽  
Mi Yang ◽  
Xiaoqing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Expression Profile ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Regulatory Pathways ◽  
Chronic Lung Diseases ◽  
Potential Biomarker

AbstractPulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

scholarly journals Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Yushi Zheng ◽  
Zhiping Lin ◽  
Xiaodi Li ◽  
Xiaoling Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Methyl Transferase ◽  
Cox Proportional Hazard Regression

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.

scholarly journals Significant correlation between HSPA4 and prognosis and immune regulation in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12315
Author(s):  
Bing-Bing Shang ◽  
Jun Chen ◽  
Zhi-Guo Wang ◽  
Hui Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Roc Curve ◽  
Immune Regulation ◽  
Immune Cell ◽  
Genetic Alterations ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Cancer Stage

Background Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Heat shock proteins (HSPs) are involved in the occurrence, progression, and immune regulation of tumors. Therefore, HSPs have been considered potential therapeutic targets. Here, we aimed to elucidate the value of HSP family A (Hsp70) member 4 (HSPA4) in the diagnosis and predicting prognosis of HCC, and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Gene mutation, DNA methylation, and the pathway involved in HCC were also analyzed. Methods The gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to compare HSPA4 expression, and the results were confirmed by immunohistochemical staining of clinical samples. R package was used to analyze the correlation between HSPA4 and cancer stage, and to establish receiver operating characteristic (ROC) curve of diagnosis, time-dependent survival ROC curve, and a nomogram model. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation, and their effect on prognosis. The Tumor Immune Estimation Resource (TIMER) was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. The STRING database was used to analyze protein–protein interaction network information. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of HSPA4 and its functional partner genes. Results Overexpression of HSPA4 was identified in 25 cancers. Overexpression of HSPA4 considerably correlated with cancer stage and alpha-fetoprotein (AFP) level in HCC. Patients with higher HSPA4 expression showed poorer prognosis. HSPA4 expression can accurately identify tumor from normal tissue (AUC = 0.957). The area under 1-, 3-, and 5-year survival ROCs were above 0.6. The HSPA4 genetic alteration rate was 1.3%. Among the 14 DNA methylation CpG sites, seven were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. The KEGG pathway enrichment analysis revealed HSPA4 enrichment in antigen processing and presentation together with HSPA8 and HSP90AA1. We verified the value of HSPA4 in the diagnosis and predicting prognosis of HCC. HSPA4 may not only participate in the occurrence and progression but also the immune regulation of HCC. Therefore, HSPA4 can be a potential diagnostic and prognostic biomarker and a therapeutic target for HCC.

scholarly journals Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

2020 ◽  
Author(s):  
Mohsen Ahmadi ◽  
Negin Saffarzadeh ◽  
Mohammad Amin Habibi ◽  
Fatemeh Hajiesmaeili ◽  
Nima Rezaei
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Methylation Status ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Survival Outcomes ◽  
Immune Cell Infiltration ◽  
Ace2 Gene

AbstractNovel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.

Comprehensive analysis of epigenetic modifications and immune-cell infiltration in tissues from patients with systemic lupus erythematosus

Epigenomics ◽  
2021 ◽  
Author(s):  
Zhenghao He ◽  
Shihang Zhou ◽  
Ming Yang ◽  
Zhidan Zhao ◽  
Yang Mei ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Epigenetic Modifications ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Methylation Analysis ◽  
Systemic Lupus ◽  
Dna Methylation Analysis

Aim: To explore potential abnormal epigenetic modifications and immune-cell infiltration in tissues from systemic lupus erythematosus (SLE) patients. Materials & methods: To utilize bioinformatics analysis and ‘wet lab' methods to identify and verify differentially expressed genes in multiple targeted organs in SLE. Results: Seven key genes, IFI44, IFI44L, IFIT1, IFIT3, PLSCR1, RSAD2 and OAS2, which are regulated by epigenetics and may be involved in the pathogenesis of SLE, are identified by combined long noncoding RNA–miRNA–mRNA network analysis and DNA methylation analysis. The results of quantitative reverse transcription PCR, immunohistochemistry and DNA methylation analysis confirmed the potential of these genes as biomarkers. Conclusion: This study reveals the potential mechanisms in SLE from epigenetic modifications and immune-cell infiltration, providing diagnostic biomarkers and therapeutic targets for SLE.

scholarly journals Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhenqing Li ◽  
Bo Ding ◽  
Jianxun Xu ◽  
Kai Mao ◽  
Pengfei Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Drug Sensitivity ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes

Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value&lt;0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.

Effects of ASCL1 expression on tumorigenesis and immune cell infiltration in a syngenic mouse model of lung adenocarcinoma

2019 ◽  
Author(s):  
Naoya Miyashita ◽  
Masafumi Horie ◽  
Yu Mikami ◽  
Hirokazu Urushiyama ◽  
Kensuke Fukuda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration
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