Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Takemoto, Akira; Tanimoto, Kousuke; Mori, Seiichi; Inoue, Jun; Fujiwara, Naoto; Noda, Tetsuo; Inazawa, Johji

doi:10.1111/cas.15063

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…As reported previously, the MPP subtypes tended to show an aggregation of characteristic mutations (EGFR, KRAS, and BRAF) [ 27 , 38 ]; we also observed more frequent mutations in the RTK/Ras, Notch, and Wnt pathways and an enrichment of the AID/APOBEC mutation signature in MPP. Similar to the overall landscape of esophageal, head and neck, and penile squamous cell carcinomas [ 39 , 40 , 41 ], the MPP showed both enrichment of the Notch pathway mutations and a substitution of the APOBEC-related signature in the presence of high genomic variation. Combined, these findings imply a strong association between these two factors in tumor development.…”

Section: Discussionmentioning

confidence: 79%

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Meng

Zhang

Wang

et al. 2022

Cancers

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Background: Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions. Methods: We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD. Results: The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component’s progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort. Conclusions: Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.

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Section: Discussionmentioning

confidence: 79%

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Meng

Zhang

Wang

et al. 2022

Cancers

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“…Previous studies have demonstrated that CNVs and DNA methylation can reduce mRNA levels [ 31 , 32 ], which correlates closely with patient prognosis. We also systematically analyzed the relationship between XCL2, DNA methylation, and CNVs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis reveals XCL2 as a cancer prognosis and immune infiltration-related biomarker

Chen,

Zou,

Song

et al. 2023

Aging

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Background: X-C Motif Chemokine Ligand 2 (XCL2) is a 114 amino acid, structurally conserved chemokine involved in activating cytotoxic T cells. However, the pathophysiological mechanisms of XCL2 protein in various disease conditions, particularly cancer, remain poorly understood. Methods: Bioinformatics was used to detect the expression of XCL2, the relationship between survival time and XCL2 in BLCA patients, the mutational status of XCL2, the role of XCL2 in the tumor immune microenvironment, and the sensitivity of XCL2-targeted drugs in 33 cancers. In vitro experiments were conducted to investigate the chemotactic effects of XCL2 expression on M1-type macrophages in human specimens and in isolated cancer cells. Results: XCL2 expression was downregulated in tumor tissues and closely associated with the prognosis of human cancers. Furthermore, XCL2 affects DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) in human cancers. The expression level of XCL2 significantly correlated with infiltrated immune cells, immunological pathways, and other immune markers. More importantly, we found that XCL2 was positively associated with T lymphocytes and macrophages in the transcriptome and single-cell sequencing data. Using multiple immunofluorescence staining, we found that the expression level of XCL2 was upregulated in many cells in pan-cancer samples, and the number of M1 macrophage marker CD68 and INOS-positive cells increased. 786O, U251, and MDA-MB-231 cells could recruit more M1 macrophages in vitro after overexpressing XCL2. Conclusions: Our results reveal that XCL2 could act as a vital chemokine in pan-cancer and provide new targets and concepts for cancer treatment.

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“…Increasing evidence has demonstrated that genetic alteration and DNA modifications can significantly affect gene expression in cancers [ 24 , 25 ]. Our analysis showed that copy number variation (CNV) and DNA methylation were significantly related to IL18RAP expression levels.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immunological roles of IL18RAP in human cancers

Chen,

Song,

Zou

et al. 2023

Aging

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Across several cancers, IL18 receptor accessory protein (IL18RAP) is abnormally expressed, and this abnormality is related to tumor immunity and heterogeneous clinical outcomes. In this study, based on bioinformatics analysis, we discovered that IL18RAP is related to the human tumor microenvironment and promotes various immune cells infiltration. Additionally, the multiple immunofluorescence staining revealed that with the increased expression of IL18RAP, the number of infiltrated M1 macrophages increased. This finding was confirmed by coculture migration analysis using three human cancer cell lines (MDA-MB-231, U251, and HepG2) with IL18RAP knockdown. We discovered a positive link between IL18RAP and the majority of immunostimulators, immunoinhibitors, major histocompatibility complex (MHC) molecules, chemokines, and chemokine receptor genes using Spearman correlation analysis. Additionally, functional IL18RAP’s gene set enrichment analysis (GSEA) revealed that it is related to a variety of immunological processes, such as positive regulation of interferon gamma production and positive regulation of NK cell-mediated immunity. Moreover, we used single-cell RNA sequencing analysis to detect that IL18RAP was mainly expressed in immune cells, and HALLMARK analysis confirmed that the INF-γ gene set expression was upregulated in CD8Tex cells. In addition, in human and mouse cancer cohorts, we found that the level of IL18RAP can predict the immunotherapy response. In short, our study showed that IL18RAP is a new tumor biomarker and may become a potential immunotherapeutic target in cancer.

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Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 9 publications

References 44 publications

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Comprehensive analysis reveals XCL2 as a cancer prognosis and immune infiltration-related biomarker

Prognostic and immunological roles of IL18RAP in human cancers

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