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.
Highlights
Breast cancer is the most common malignant disease affecting women worldwide [1]
We examined the difference in Sirtuin 7 (SIRT7) expression between tumor and adjacent normal tissues by using RNA-seq data from multiple malignancies in The Cancer Genome Atlas (TCGA)
From the Tumor Immune Estimation Resource (TIMER) database, we found that SIRT7 was upregulated in breast cancer, cholangiocarcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, thyroid carcinoma, and uterine corpus endometrial carcinoma, while it has lower expression levels in colon adenocarcinoma and kidney chromophobe cancers compared with adjacent healthy tissues
Summary
Breast cancer is the most common malignant disease affecting women worldwide [1]. Most breast cancer-related deaths are caused by metastases [2]. Based on gene expression profiles, breast cancer is classified into three main subtypes: luminal (luminal A and luminal B), human epidermal growth factor receptor (HER2)-positive, and triple-negative breast cancer (TNBC) [3]. A large number of patients experienced relapse due to organ metastases, especially those with the worst TNBC prognosis [4]. Surgery, radiotherapy, chemotherapy, endocrine therapy, and other combined therapies are commonly used in the clinic with certain effects [6]. These conventional therapies work only at the early stages but not that effective for patients at advanced stages or with distant metastasis. The prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear
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