Multiomics characteristics of neurogenesis-related gene are dysregulated in tumor immune microenvironment

Wang, Ben; Mou, Hai; Liu, Mengmeng; Ran, Zhujie; Li, Xin; Li, Jie; Ou, Yunsheng

doi:10.1038/s41525-021-00202-y

Cited by 10 publications

(5 citation statements)

References 66 publications

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“…However, the immune hot type of IS1 had a better survival prognosis than IS5. Moreover, the hot or cold of a tumor was not the only factor that determined the effectiveness of immunotherapy, unlike previous research that only divided tumor cells into the immune cold and hot types [ 23 ]. Our analysis further stratified HCC into 5 immune subgroups, and IS4 with the best prognosis was characterized by immune activity and antitumor genesis.…”

Section: Discussionmentioning

confidence: 99%

The Association between Immune Subgroups and Gene Modules for the Clinical, Cellular, and Molecular Characteristic of Hepatocellular Carcinoma

Chen

Zhu

et al. 2022

Journal of Oncology

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The heterogeneity of hepatocellular carcinoma (HCC) is related to immune cell infiltration and genetic aberrations in the tumor microenvironment. This study aimed to identify the novel molecular typing of HCC according to the genetic and immune characteristics, to obtain accurate clinical management of this disease. We performed consensus clustering to divide 424 patients into different immune subgroups and assessed the reproducibility and efficiency in two independent cohorts with 921 patients. The associations between molecular typing and molecular, cellular, and clinical characteristics were investigated by a multidimensional bioinformatics approach. Furthermore, we conducted graph structure learning-based dimensionality reduction to depict the immune landscape to reveal the interrelation between the immune and gene systems in molecular typing. We revealed and validated that HCC patients could be segregated into 5 immune subgroups (IS1-5) and 7 gene modules with significantly different molecular, cellular, and clinical characteristics. IS5 had the worst prognosis and lowest enrichment of immune characteristics and was considered the immune cold type. IS4 had the longest overall survival, high immune activity, and antitumorigenesis, which were defined as the immune hot and antitumorigenesis types. In addition, immune landscape analysis further revealed significant intraclass heterogeneity within each IS, and each IS represented distinct clinical, cellular, and molecular characteristics. Our study provided 5 immune subgroups with distinct clinical, cellular, and molecular characteristics of HCC and may have clinical implications for precise therapeutic strategies and facilitate the investigation of immune mechanisms in HCC.

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Section: Discussionmentioning

confidence: 99%

The Association between Immune Subgroups and Gene Modules for the Clinical, Cellular, and Molecular Characteristic of Hepatocellular Carcinoma

Chen

Zhu

et al. 2022

Journal of Oncology

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“…ScRNA-seq analysis is a powerful tool for characterizing the distribution and functional enrichment of various cell subtypes in the tumor microenvironment [ 53 , 54 ]. Michael et al [ 55 ] revealed hundreds of molecularly diverse cell types in the nervous system using single-cell sequencing.…”

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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“…Wang et al identified several molecular differences between inflamed and noninflamed TMEs using scRNA-seq. These results have profound clinical implications as they may be helpful to the optimization of current combination immunotherapy (54). We also performed scRNA-seq to describe the landscape of PDIA5 in cell subpopulations within diverse cancer types.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Immunological Role of PDIA5: A Potential Target for Immunotherapy

Chen

et al. 2022

Front. Immunol.

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The aberrant protein disulfide isomerase A5 (PDIA5) expression was relevant to the poor prognosis of patients with human cancers. However, its relationship with the epigenetic and genetic alterations and its effect on tumor immunity is still lacking. In the present study, we comprehensively analyzed the immune infiltration role of PDIA5 in human cancers based on large-scale bioinformatics analyses and in vitro experiments. Obvious DNA methylation and moderate alteration frequency of PDIA5 were observed in human cancers. The expression level of PDIA5 was significantly correlated with infiltrated immune cells, immune pathways, and other immune signatures. We found that cancer cells and macrophages exhibited high PDIA5 expression in human cancers using the single-cell RNA sequencing analysis. We also demonstrated the interaction between PDIA5 and immune cells in glioblastoma multiforme (GBM). Multiplex immunofluorescence staining showed the upregulated expression level of PDIA5 and the increased number of M2 macrophage markers-CD163 positive cells in pan-cancer samples. Notably, PDIA5 silencing resulted in upregulated expression of PD-L1 and SPP1 in U251 cells. Silencing of PDIA5 in hepG2 cells, U251 cells, and PC3 cells contributed to a decline in their ability of proliferation, clone formation, and invasion and inhibited the migration of cocultured M2 macrophages. Additionally, PDIA5 also displayed predictive value in the immunotherapy response of both murine and human cancer cohorts. Overall, our findings indicated that PDIA5 might be a potential target for immunotherapies in cancers.

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Multiomics characteristics of neurogenesis-related gene are dysregulated in tumor immune microenvironment

Cited by 10 publications

References 66 publications

The Association between Immune Subgroups and Gene Modules for the Clinical, Cellular, and Molecular Characteristic of Hepatocellular Carcinoma

The Association between Immune Subgroups and Gene Modules for the Clinical, Cellular, and Molecular Characteristic of Hepatocellular Carcinoma

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

Pan-Cancer Analysis of the Immunological Role of PDIA5: A Potential Target for Immunotherapy

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