High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

Frontiers in Oncology

Oncology

Ziming Xing¹  Haihua Yang²  Xuequan Wang²  Qiupeng Wang²  Tongjing Xing²  Huazhong Chen² 

[1]Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China

[2]Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China

关键词: hepatocellular carcinoma;    nectin-1;    prognostic;    cell proliferation;    metastasis;   

DOI  :  10.3389/fonc.2022.953529

 received in 2022-05-26, accepted in 2022-07-22,  发布年份 2022

来源: Frontiers

【 摘 要 】

ObjectivesNectins 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).MethodsThe 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.ResultsThe 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.ConclusionsAbnormal 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.

【 授权许可】

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Copyright © 2022 Wang, Xing, Chen, Yang, Wang and Xing