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通过综合生物信息学分析鉴定作为参与乳腺癌免疫浸润的潜在治疗靶点。

Identification of as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis.

作者信息

Huo Qin, Ning Lvwen, Xie Ni

机构信息

Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen, People's Republic of China.

出版信息

Breast Cancer (Dove Med Press). 2023 Mar 10;15:213-226. doi: 10.2147/BCTT.S400808. eCollection 2023.

Abstract

PURPOSE

Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed expression and its prognostic value in breast cancer with immune cell infiltration.

PATIENTS AND METHODS

Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of expression for breast cancer. The co-expression pattern of was assessed by the LinkedOmics web portal. The relationship between expression and immune cells was analyzed using the TIMER database. The correlation between and lymphocytes and immunomodulators was established with the TISIDB database.

RESULTS

There was a lower expression in breast cancer tissue than in normal tissue. Interestingly, expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with expression in breast cancer.

CONCLUSION

expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. may be considered a promising therapeutic target for patients with breast cancer.

摘要

目的

颗粒酶A(GZMA)是多种癌症类型潜在的预后靶点。然而,其在伴有免疫浸润的乳腺癌中的治疗意义仍存在争议。我们分析了其在伴有免疫细胞浸润的乳腺癌中的表达及其预后价值。

患者与方法

数据来自于癌症基因组图谱登记的乳腺癌患者。对其表达与患者的临床病理特征(如年龄、病理分期、转移分期、总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI))进行相关性分析。采用Kaplan-Meier分析和Cox比例风险回归模型来检验其表达对乳腺癌的预测意义。通过LinkedOmics网站评估其共表达模式。使用TIMER数据库分析其表达与免疫细胞之间的关系。通过TISIDB数据库建立其与淋巴细胞和免疫调节剂之间的相关性。

结果

乳腺癌组织中的表达低于正常组织。有趣的是,其表达与年龄、病理分期以及肿瘤、淋巴结和转移分期相关。其过表达也与更好的OS、DSS和PFI相关。基于Cox回归分析,其被确定为乳腺癌独立的有利预后因素。我们的研究结果表明,在乳腺癌中其与T细胞检查点(程序性死亡受体1(PD-1)、程序性死亡受体配体1(PD-L1)和细胞毒性T淋巴细胞相关抗原4(CTLA-))之间存在密切关联。此外,我们使用定量免疫荧光评估了其表达与树突状细胞和CD8 + T细胞标志物之间的相互作用。我们发现,树突状细胞和CD8 + T细胞浸润增加与乳腺癌中的表达相关。

结论

其表达与乳腺癌的良好预后相关,并且与免疫细胞浸润显著相关。它可能被认为是乳腺癌患者有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2814/10013577/bd0b48127ce3/BCTT-15-213-g0001.jpg

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