ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

Liu, Jiazhou; Wei, Yu; Wu, Yushen; Li, Jie; Sun, Jiazheng; Ren, Guosheng; Li, Hongzhong

doi:10.3389/fimmu.2021.657950

Cited by 11 publications

(16 citation statements)

References 42 publications

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“…M1 macrophages secrete cytokines, killing tumor cells in the TME. M2 macrophages secrete anti-inflammatory factors, it could promote tumor growth and metastasis [ 38 ]. Our study showed that more M1 macrophages infiltrated in CFB high-expression group, which implied that tumor-infiltrated macrophages exerted immune functions to exhibit anti-tumor effects.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

Shi

Sun

et al. 2021

Bioengineered

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Stromal and immune cells are major components of tumor microenvironment (TME) and affect the growth and development of thyroid carcinoma (THCA). However, data on the exact mechanisms that define the relationship between the TME and THCA remain scant. We calculated stromal and immune cells scores and the proportion of tumor-infiltrating immune cells (TICs) by CIBERSORT and ESTIMATE based on the THCA gene expression data from the Cancer Genome Atlas (TCGA). In addition, we evaluated differentially expressed genes (DEGs) from high- and low-score groups and performed functional enrichment analysis. Furthermore, our data show a significant correlation between plasma complement factor B (CFB) and PTC development and prognosis. Gene Set Enrichment Analysis (GSEA) demonstrated that the CFB was mainly enriched in immune response pathways. The expression of CFB was positively correlated with T cells CD8, Macrophages M1, Plasma cells, T cells CD4 memory activated, T cells follicular helper and T cells regulatory (Tregs), whereas negatively correlated with Eosinophils, Macrophages M0, Macrophages M2, Mast cells resting, T cells CD4 memory resting in the TME. Finally, the expression level of CFB was verified by other cohorts from Gene Expression Omnibus (GEO) database and quantitative Real-Time PCR (qRT-PCR) analyses, which was consistent with the results of bioinformatic analysis. Taken together, our data demonstrated that the CFB could be a prognostic marker for THCA and its expression influences the infiltration of immune cells.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

Shi

Sun

et al. 2021

Bioengineered

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“…GSEA 4.1.0 software (downloaded from http://www.gsea-msigdb.org/gsea/downloads.jsp ) was employed to dissect the signaling pathways significantly associated with NPY5R expression levels. The pathways with the following criteria were regarded to be significantly enriched: nominal p -value < 0.05, false discovery rate (FDR) q -value < 0.25, and normalized enrichment score (NES) > 1 ( Liu et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy

Liu

Wang

Sun

et al. 2022

Front. Cell Dev. Biol.

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Breast cancer (BC) is the most common tumor in women, and the molecular mechanism underlying its pathogenesis remains unclear. In this study, we aimed to investigate gene modules related to the phenotypes of BC, and identify representative candidate biomarkers for clinical prognosis of BC patients. Using weighted gene co-expression network analysis, we here identified NPY5R as a hub gene in BC. We further found that NPY5R was frequently downregulated in BC tissues compared with adjacent tumor-matched control tissues, due to its aberrant promoter CpG methylation which was confirmed by methylation analysis and treatment with demethylation agent. Higher expression of NPY5R was closely associated with better prognosis for BC patients. Gene set enrichment analysis showed that transcriptome signatures concerning apoptosis and cell cycle were critically enriched in specimens with elevated NPY5R. Ectopic expression of NPY5R significantly curbed breast tumor cell growth, induced cell apoptosis and G2/M arrest. Moreover, NPY5R also promoted the sensitivity of BC cells to doxorubicin. Mechanistically, we found that NPY5R restricted STAT3 signaling pathway activation through interacting with IL6, which may be responsible for the antitumor activity of NPY5R. Collectively, our findings indicate that NPY5R functions as a tumor suppressor but was frequently downregulated in BC.

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“…Similar observations have been made in breast cancer analyses. In one breast cancer study, ATP2C2 was upregulated compared to normal tissue [ 152 ]. In a separate set of breast cancer samples, SPCA2 knockdown enhanced sensitivity to DNA-damaging agents, including doxorubicin, cisplatin, and ionizing radiation [ 153 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma

Cutliffe

McKenna

Chandrashekar

et al. 2021

Exploration of Targeted Anti-Tumor Therapy

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Aim: To investigate alterations in transcription of genes, encoding Ca2+ toolkit proteins, in oesophageal adenocarcinoma (OAC) and to assess associations between gene expression, tumor grade, nodal-metastatic stage, and patient survival. Methods: The expression of 275 transcripts, encoding components of the Ca2+ toolkit, was analyzed in two OAC datasets: the Cancer Genome Atlas [via the University of Alabama Cancer (UALCAN) portal] and the oesophageal-cancer, clinical, and molecular stratification [Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS)] dataset. Effects of differential expression of these genes on patient survival were determined using Kaplan-Meier log-rank tests. OAC grade- and metastatic-stage status was investigated for a subset of genes. Adjustment for the multiplicity of testing was made throughout. Results: Of the 275 Ca2+-toolkit genes analyzed, 75 displayed consistent changes in expression between OAC and normal tissue in both datasets. The channel-encoding genes, N-methyl-D-aspartate receptor 2D (GRIN2D), transient receptor potential (TRP) ion channel classical or canonical 4 (TRPC4), and TRP ion channel melastatin 2 (TRPM2) demonstrated the greatest increase in expression in OAC in both datasets. Nine genes were consistently upregulated in both datasets and were also associated with improved survival outcomes. The 6 top-ranking genes for the weighted significance of altered expression and survival outcomes were selected for further analysis: voltage-gated Ca2+ channel subunit α 1D (CACNA1D), voltage-gated Ca2+ channel auxiliary subunit α2 δ4 (CACNA2D4), junctophilin 1 (JPH1), acid-sensing ion channel 4 (ACCN4), TRPM5, and secretory pathway Ca2+ ATPase 2 (ATP2C2). CACNA1D, JPH1, and ATP2C2 were also upregulated in advanced OAC tumor grades and nodal-metastatic stages in both datasets. Conclusions: This study has unveiled alterations of the Ca2+ toolkit in OAC, compared to normal tissue. Such Ca2+ signalling findings are consistent with those from studies on other cancers. Genes that were consistently upregulated in both datasets might represent useful markers for patient diagnosis. Genes that were consistently upregulated, and which were associated with improved survival, might be useful markers for patient outcome. These survival-associated genes may also represent targets for the development of novel chemotherapeutic agents.

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ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

Cited by 11 publications

References 42 publications

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy

Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma

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