Chordin-like 1 is a novel prognostic biomarker and correlative with immune cell infiltration in lung adenocarcinoma

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.

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Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma

10.21203/rs.3.rs-105348/v1 ◽

2020 ◽

Author(s):

Lianxiang Luo ◽

Yushi Zheng ◽

Zhiping Lin ◽

Xiaodi Li ◽

Xiaoling Li ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Immune Cell ◽

Prognostic Biomarker ◽

Tumor Infiltrating Lymphocytes ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Kaplan Meier ◽

Online Databases ◽

Cox Proportional Hazard Regression

Abstract Background: The role of Serine hydroxymethyltransferase2 (SHMT2) in diverse cancers has attracted increasing attention. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is yet to be studied.Methods: The data of mRNA and clinic 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 infiltrates in LUAD.Results: The mRNA expression and protein expression of SHMT2 in LUAD were higher than normal tissue. A Kaplan-Meier analysis showed the 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 for patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD.Conclusions: These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of phenotypes of immune cell infiltration in LUAD.

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ZC3H12D is a prognostic biomarker associated with immune cell infiltration in lung adenocarcinoma

Translational Cancer Research ◽

10.21037/tcr-20-1465 ◽

2020 ◽

Vol 9 (10) ◽

pp. 6128-6142

Author(s):

Wangang Gong ◽

Wumin Dai ◽

Haibin Wei ◽

Yongyi Chen ◽

Zhiguo Zheng

Keyword(s):

Lung Adenocarcinoma ◽

Immune Cell ◽

Prognostic Biomarker ◽

Cell Infiltration ◽

Immune Cell Infiltration

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ARNTL2, an Immunoregulation-Related Prognostic Biomarker in Pan-Cancer and Lung Adenocarcinoma

10.21203/rs.3.rs-1065822/v1 ◽

2021 ◽

Author(s):

Gujie Wu ◽

Wenmiao Wang ◽

Zheng Yang ◽

Qun Xue

Keyword(s):

Lung Adenocarcinoma ◽

Immune Cell ◽

Prognostic Biomarker ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Cancer Drugs ◽

Anti Cancer ◽

Pan Cancer

Abstract Background ARNTL2 is a member of the PAS superfamily that promotes tumor progression. However, the role of ARNTL2 in lung adenocarcinoma (LUAD) remains unclear. The purpose of our study was to investigate the function of ARNTL2 in LUAD. Methods The expression, clinical features, and prognostic role of ARNTL2 in pan-cancer were evaluated using The Cancer Genome Atlas and Genotype-Tissue Expression data. GSEA and GSVA of ARNTL2 were performed using the R package “clusterProfiler.” The correlation between immune cell infiltration level and ARNTL2 expression was analyzed using two sources of immune cell infiltration data, including the TIMER2 and ImmuCellAI database. Finally,we analyzed the correlation between ARNTL2 and IC50 of 192 drugs. Results ARNTL2 was substantially overexpressed in LUAD and pan-cancer. High ARNTL2 expression predicted poor survival in patients with LUAD. We also found that ARNTL2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as tumor associated macrophages, cancer associated fibroblasts and Tregs. Among the 192 anti-cancer drugs, ARNTL2 expression was positively correlated with IC50 of 114 anti-cancer drugs, such as SB505124, Doramapimod, Nutlin-3a (-), Sabutoclax, AZD5991, PF-4708671, Elephantin, PRIMA-1MET, Sorafenib, Vorinostat, and MK-2206. Conclusions Our results revealed that ARNTL2 is a potential prognostic biomarker in LUAD. An elevated ARNTL2 expression indicates an immunosuppressive microenvironment, and targeted therapies against ARNTL2 have excellent potential.

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

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02995-4 ◽

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.

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DNASE1L3 as a Prognostic Biomarker Associated with Immune Cell Infiltration in Cancer

OncoTargets and Therapy ◽

10.2147/ott.s294332 ◽

2021 ◽

Vol Volume 14 ◽

pp. 2003-2017

Author(s):

Zenghua Deng ◽

Mengmeng Xiao ◽

Dexiao Du ◽

Nan Luo ◽

Dongfang Liu ◽

...

Keyword(s):

Immune Cell ◽

Prognostic Biomarker ◽

Cell Infiltration ◽

Immune Cell Infiltration

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CKS2 Overexpression Correlates with Prognosis and Immune Cell Infiltration in Lung Adenocarcinoma: A Comprehensive Study based on Bioinformatics and Experiments

Journal of Cancer ◽

10.7150/jca.63625 ◽

2021 ◽

Vol 12 (23) ◽

pp. 6964-6978

Author(s):

Zhiping Wang ◽

Mengyan Zhang ◽

Yahua Wu ◽

Yilin Yu ◽

Qunhao Zheng ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Comprehensive Study

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

Frontiers in Oncology ◽

10.3389/fonc.2020.580027 ◽

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<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.

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.231 ◽

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.

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