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SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.

ABSTRACT: Background: Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear. Methods: The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein Atlas (HPA), UALCAN, Breast Cancer Gene-Expression Miner (BC-GenExMiner), and Kaplan-Meier plotter databases. Also, the expression correlations between SIRT7 and immune infiltration gene markers were analyzed using TIMER and further verified the results using immunohistochemistry. Results: SIRT7 exhibited higher expression levels in breast cancer tissues than the adjacent normal tissues. SIRT7 expression was significantly correlated with sample type, subclass, cancer stage, menopause status, age, nodal status, estrogen receptor (ER), progesterone receptor (PR), and triple-negative status. High SIRT7 expression was associated with poor prognosis in breast cancer-luminal A [overall survival (OS): hazard ratio (HR) = 1.54, p = 1.70e-02; distant metastasis-free survival (DMFS): HR = 1.56, p = 2.60e-03]. Moreover, the expression of SIRT7 was positively correlated with the expression of IRF5 (M1 macrophages marker, r = 0.165, p = 1.13e-04) and PD1 (T cell exhaustion marker, r = 0.134, p = 1.74e-03). These results suggested that the expression of SIRT7 was related to M1 macrophages and T cell exhaustion infiltration in breast cancer-luminal. Conclusions: These findings demonstrate that the high expression of SIRT7 indicates poor prognosis in breast cancer as well as increased immune infiltration levels of M1 macrophages and T cell exhaustion in breast cancer-luminal. Thus, SIRT7 may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in breast cancer-luminal.

SUBMITTER: Huo Q

PROVIDER: S-EPMC7247806 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.

Huo Qin Q Li Zhenwei Z Cheng Lixin L Yang Fan F Xie Ni N

Frontiers in oncology 20200512

<b>Background:</b> Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear. <b>Methods:</b> The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein ...[more]

PMID: 32528869

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Project description:Background: This study aimed to explore the prognostic value of angiogenesis-related genes (ARGs) and their association with immune cell infiltration (ICI) in breast cancer (BC). Methods: Transcriptome data of BC were obtained from the TCGA and GEO databases. Differentially expressed ARGs were identified by the limma package. The identification of key genes and construction of the risk score model were performed by univariate and multivariate Cox regression algorithms. The prognostic value of the risk score was assessed by ROC curves and nomogram. GO, KEGG pathway, and GSEA were used to investigate the biological functions of differentially expressed genes (DEGs), and CIBERSORT, ssGSEA, and xCell algorithms were performed to estimate the ICI in high-risk and low-risk groups. The correlations between prognostic biomarkers and differentially distributed immune cells were assessed. Moreover, a ceRNA regulatory network based on prognostic biomarkers was constructed and visualized by Cytoscape software. Results: A total of 18 differentially expressed ARGs were identified between tumor and adjacent normal tissue samples. TNFSF12, SCG2, COL4A3, and TNNI3 were identified as key prognostic genes by univariate and multivariate Cox regression analyses. The risk score model was further constructed based on the four-gene signature and validated in GSE7390 and GSE88770 datasets. ROC curves and nomogram indicated that the risk score had good accuracy for determining BC patient survival. Biological function analysis showed that DEGs in high- and low-risk groups had a high enrichment in immune-related biological processes and signaling pathways. Moreover, significantly different ICIs were found between high- and low-risk groups, such as memory B cells, CD8+ T cells, resting memory CD4+ T cells, follicular helper T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils, and each prognostic biomarker was significantly correlated with one or more immune cell types. Conclusion: The current study identified novel prognostic ARGs and developed a prognostic model for predicting survival in patients with BC. Furthermore, this study indicated that ICI may act as a bond between angiogenesis and BC. These findings enhance our understanding of angiogenesis in BC and provide novel guidance on developing therapeutic targets for BC patients.

Project description:Background ZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear. Methods The expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan–Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining. Results The combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues. Conclusions These findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD.

Dataset Information

SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.

Publications

SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.

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