Wang Xuequan, Xing Ziming, Chen Huazhong, Yang Haihua, Wang Qiupeng, Xing Tongjing
Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Front Oncol. 2022 Aug 18;12:953529. doi: 10.3389/fonc.2022.953529. eCollection 2022.
Nectins are a new class of cell-adhesion molecules that play an important role in tumorigenesis and disease progression. The aim of this study was to investigate the prognostic and pathogenetic roles of nectins in hepatocellular carcinoma (HCC).
The expression levels of the nectin family in HCC and their role in prognosis were analyzed by bioinformatics analysis based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma database. The correlations between nectins and immune cells were analyzed using TIMER. The functional enrichment of the nectin-1 coexpression network was evaluated in TCGA cohort, and the expression levels of nectin-1 were detected by immunohistochemistry and Western blot analysis. A Transwell kit was used for cell migration experiments. Cell proliferation was analyzed using Cell Counting Kit-8.
The expression levels of nectin-1 protein in the cancer tissues of 28 patients with HCC were higher than those in paracancerous tissues. The Kaplan-Meier plotter analysis showed that the high expression of all nectin family numbers was related to the poor prognosis of HCC patients. The abnormal expression of nectin-1 effectively distinguished the prognosis at different stages and grades of HCC. The high expression of 17 methylation sites of the nectin-1 gene was related to the high overall survival of HCC patients. Kyoto Encyclopedia of Genes and Genomes analysis of genes negatively correlated with nectin-1, revealing their close relation to the regulation of the immune-effector process. Pearson's correlation analysis showed that nectin-1 was significantly positively correlated with multiple immune genes and B cells, CD4 T cells, macrophages, neutrophils, and dendritic cell infiltration. Cell proliferation of the knockdown (KD) group decreased significantly compared to the NC-KD group. The number of metastatic cells in the KD group decreased significantly compared to that in the NC-KD group.
Abnormal expression of nectins and multiple methylation sites closely correlates with poor prognosis in HCC patients. Nectins are related to immune cell infiltration and immune-related genes. In particular, nectin-1 can promote the proliferation and migration of liver cancer cells and distinguish the prognosis at different stages and grades of HCC. Nectin-1 might be a new potential molecular marker for prognostic evaluation and also a therapeutic target for HCC.
NECTIN是一类新型细胞黏附分子，在肿瘤发生和疾病进展中起重要作用。本研究旨在探讨NECTIN在肝细胞癌（HCC）中的预后及发病机制作用。
基于癌症基因组图谱（TCGA）肝细胞癌数据库，通过生物信息学分析，分析NECTIN家族在HCC中的表达水平及其在预后中的作用。使用TIMER分析NECTIN与免疫细胞之间的相关性。在TCGA队列中评估NECTIN-1共表达网络的功能富集情况，并通过免疫组织化学和蛋白质印迹分析检测NECTIN-1的表达水平。使用Transwell试剂盒进行细胞迁移实验。使用细胞计数试剂盒-8分析细胞增殖情况。
28例HCC患者癌组织中NECTIN-1蛋白表达水平高于癌旁组织。Kaplan-Meier生存曲线分析显示，所有NECTIN家族成员的高表达均与HCC患者的不良预后相关。NECTIN-1的异常表达可有效区分不同分期和分级HCC的预后。NECTIN-1基因17个甲基化位点的高表达与HCC患者的高总生存率相关。对与NECTIN-1呈负相关的基因进行京都基因与基因组百科全书分析，揭示它们与免疫效应过程调控密切相关。Pearson相关性分析显示，NECTIN-1与多种免疫基因以及B细胞、CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞浸润显著正相关。与NC-KD组相比，敲低（KD）组的细胞增殖显著降低。与NC-KD组相比，KD组的转移细胞数量显著减少。
NECTIN的异常表达和多个甲基化位点与HCC患者的不良预后密切相关。NECTIN与免疫细胞浸润和免疫相关基因有关。特别是，NECTIN-1可促进肝癌细胞的增殖和迁移，并区分不同分期和分级HCC的预后。NECTIN-1可能是一种新的潜在预后评估分子标志物，也是HCC的治疗靶点。
