Stemness Related Genes Revealed by Network Analysis Associated With Tumor Immune Microenvironment and the Clinical Outcome in Lung Adenocarcinoma

Zeng, Hao; Ji, Jianrui; Song, Xindi; Huang, Yeqian; Li, Hui; Huang, Juan; Ma, Xuelei

doi:10.3389/fgene.2020.549213

Cited by 53 publications

(53 citation statements)

References 47 publications

(58 reference statements)

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“…Nowadays, widespread analysis of high-throughput technologies via advanced computational techniques facilitates the identification of disease-related biomarkers ( Fernandes et al, 2020 ). Weighted gene co-expression network analysis (WGCNA) is a well-documented systematic bioinformatics tool to extract co-related gene modules and then identify hub genes that correlated with clinical traits of interest ( Horvath and Dong, 2008 ; Kakati et al, 2019 ), and has been widely applied for potential therapeutic target detections in various cancers ( Zeng et al, 2020 ; Zhang et al, 2020 ; Zhu and Hou, 2020 ). In this study, based on RNA-seq data acquired from public database, M2 macrophage fractions in stage III/IV pMMR CRC patients were calculated by the CIBERSORT algorithm, and WGCNA was then performed to identify the associated hub genes.…”

Section: Introductionmentioning

confidence: 99%

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma

Zheng

Bai

Wang

et al. 2021

Front. Mol. Biosci.

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Immunotherapy has achieved efficacy for advanced colorectal cancer (CRC) patients with a mismatch-repair-deficient (dMMR) subtype. However, little immunotherapy efficacy was observed in patients with the mismatch repair-proficient (pMMR) subtype, and hence, identifying new immune therapeutic targets is imperative for those patients. In this study, transcriptome data of stage III/IV CRC patients were retrieved from the Gene Expression Omnibus database. The CIBERSORT algorithm was used to quantify immune cellular compositions, and the results revealed that M2 macrophage fractions were higher in pMMR patients as compared with those with the dMMR subtype; moreover, pMMR patients with higher M2 macrophage fractions experienced shorter overall survival (OS). Subsequently, weighted gene co-expression network analysis and protein–protein interaction network analysis identified six hub genes related to M2 macrophage infiltrations in pMMR CRC patients: CALD1, COL6A1, COL1A2, TIMP3, DCN, and SPARC. Univariate and multivariate Cox regression analyses then determined CALD1 as the independent prognostic biomarker for OS. CALD1 was upregulated specifically the in CMS4 CRC subtype, and single-sample Gene Set Enrichment Analysis (ssGSEA) revealed that CALD1 was significantly correlated with angiogenesis and TGF-β signaling gene sets enrichment scores in stage III/IV pMMR CRC samples. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm and correlation analysis revealed that CALD1 was significantly associated with multiple immune and stromal components in a tumor microenvironment. In addition, GSEA demonstrated that high expression of CALD1 was significantly correlated with antigen processing and presentation, chemokine signaling, leukocyte transendothelial migration, vascular smooth muscle contraction, cytokine–cytokine receptor interaction, cell adhesion molecules, focal adhesion, MAPK, and TGF-beta signaling pathways. Furthermore, the proliferation, invasion, and migration abilities of cancer cells were suppressed after reducing CALD1 expression in CRC cell lines. Taken together, multiple bioinformatics analyses and cell-level assays demonstrated that CALD1 could serve as a prognostic biomarker and a prospective therapeutic target for stage III/IV pMMR CRCs.

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Section: Introductionmentioning

confidence: 99%

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma

Zheng

Bai

Wang

et al. 2021

Front. Mol. Biosci.

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“…[ 51 ] Previous studies also studied the relationship between cancer stemness and anti‐tumor immunity and revealed that cancer stemness was negatively correlated with immune infiltration in LUAD. [ 52,53 ]…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Progression and Heterogeneity in Multiple Nodules of Lung Adenocarcinoma

Liu

Wang

et al. 2021

Small Methods

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Lung cancer remains the leading cause of cancer‐related death worldwide. Lung adenocarcinoma (LUAD) is thought to be caused by precursor lesions of atypical adenoma‐like hyperplasia and may have extensive in situ growth before infiltration. To explore the relevant factors in heterogeneity and evolution of lung adenocarcinoma subtypes, the authors perform single‐cell RNA sequencing (scRNA‐seq) on tumor and normal tissue from five multiple nodules’ LUAD patients and conduct a thorough gene expression profiling of cancer cells and cells in their microenvironment at single‐cell level. This study gives a deep understanding of heterogeneity and evolution in early glandular neoplasia of the lung. This dataset leads to discovery of the changes in the immune microenvironment during the development of LUAD, and the development process from adenocarcinoma in situ (AIS) to invasive adenocarcinoma (IAC). This work sheds light on the direction of early tumor development and whether they are homologous.

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“…One of the explanations as to why pediatric tumors are less accessible for elimination by the immune system is stemness itself. The mRNAsi has been linked with immune cell exclusion and protection of antigenic clones from elimination [ 3 , 4 , 7 ]. Embryonic, mesenchymal and induced pluripotent stem cells possess immune modulatory properties, while resistance to immune-mediated destruction is an intrinsic feature of quiescent adult tissue stem cells [ 8 ] and cancer stem cells [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Gene Expression, Stemness and Immune Microenvironment in Pediatric Tumors

Stahl

Knoll

Gentles

et al. 2021

Cancers

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Pediatric tumors frequently arise from embryonal cells, often displaying a stem cell-like (“small round blue”) morphology in tissue sections. Because recently “stemness” has been associated with a poor immune response in tumors, we investigated the association of prognostic gene expression, stemness and the immune microenvironment systematically using transcriptomes of 4068 tumors occurring mostly at the pediatric and young adult age. While the prognostic landscape of gene expression (PRECOG) and infiltrating immune cell types (CIBERSORT) is similar to that of tumor entities occurring mainly in adults, the patterns are distinct for each diagnostic entity. A high stemness score (mRNAsi) correlates with clinical and morphologic subtype in Wilms tumors, neuroblastomas, synovial sarcomas, atypical teratoid rhabdoid tumors and germ cell tumors. In neuroblastomas, a high mRNAsi is associated with shortened overall survival. In Wilms tumors a high mRNAsi correlates with blastemal morphology, whereas tumors with predominant epithelial or stromal differentiation have a low mRNAsi and a high percentage of M2 type macrophages. This could be validated in Wilms tumor tissue (n = 78). Here, blastemal areas are low in M2 macrophage infiltrates, while nearby stromal differentiated areas contain abundant M2 macrophages, suggesting local microanatomic regulation of the immune response.

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Stemness Related Genes Revealed by Network Analysis Associated With Tumor Immune Microenvironment and the Clinical Outcome in Lung Adenocarcinoma

Cited by 53 publications

References 47 publications

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma

Mechanisms of Progression and Heterogeneity in Multiple Nodules of Lung Adenocarcinoma

Prognostic Gene Expression, Stemness and Immune Microenvironment in Pediatric Tumors

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