Zhang Gang, Sun Yi, Wu Zheng-Sheng, Huang Xing
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Pathology, Anhui Medical University, Hefei, China.
Front Oncol. 2021 Nov 3;11:630257. doi: 10.3389/fonc.2021.630257. eCollection 2021.
Neuroligin 2 (NLGN2) is a well-recognized transmembrane scaffolding protein that functions in synapse development and neuronal signal transduction. It has recently been implicated in multiple diseases of peripheral ectodermal origin. However, the potential roles of NLGN2 in tumors remain ill-defined. The aim of this study was to determine the clinical relevance and prognostic value of NLGN2 in breast cancer. To this end, breast cancer datasets were extracted from TCGA and other public databases, and subjected to Kaplan-Meier potter for survival analysis, GEPIA2 for assessing the immunological relevance of NLGN2 and THPA for identifying its subcellular localization. The results were further validated by immunohistochemistry analysis of tumor tissue specimens. NLGN2 was identified as a prognostic factor in breast cancer subtypes, and its high expression correlated to a favorable survival outcome. Moreover, NLGN2 overexpression in breast cancer was significantly associated with large tumor size, lymph node metastasis, late TNM stage, and high histological grade. Interestingly, there was a significant correlation between the expression level of NLGN2 and the immunomodulatory molecules, along with increased interstitial infiltration of lymphocytes. Furthermore, NLGN2 was predominantly localized in the mitochondria of breast cancer cells. In conclusion, NLGN2 has a prognostic role and immunoregulatory potential in breast cancer, and its functions likely have a mitochondrial basis. It is a promising therapeutic target in breast cancer and should be explored further.
神经连接蛋白2（NLGN2）是一种公认的跨膜支架蛋白，在突触发育和神经元信号转导中发挥作用。最近它被认为与多种外胚层起源的外周疾病有关。然而，NLGN2在肿瘤中的潜在作用仍不明确。本研究的目的是确定NLGN2在乳腺癌中的临床相关性和预后价值。为此，从TCGA和其他公共数据库中提取乳腺癌数据集，并进行Kaplan-Meier分析以进行生存分析，利用GEPIA2评估NLGN2的免疫相关性，利用THPA确定其亚细胞定位。通过对肿瘤组织标本的免疫组织化学分析进一步验证结果。NLGN2被确定为乳腺癌亚型的一个预后因素，其高表达与良好的生存结果相关。此外，乳腺癌中NLGN2的过表达与肿瘤体积大、淋巴结转移、TNM分期晚和组织学分级高显著相关。有趣的是，NLGN2的表达水平与免疫调节分子之间存在显著相关性，同时淋巴细胞的间质浸润增加。此外，NLGN2主要定位于乳腺癌细胞的线粒体中。总之，NLGN2在乳腺癌中具有预后作用和免疫调节潜力，其功能可能基于线粒体。它是乳腺癌中一个有前景的治疗靶点，值得进一步探索。
