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水通道蛋白 9 和 Zap70 作为免疫相关的预后生物标志物抑制喉癌细胞的增殖、迁移和侵袭。

AQP9 and ZAP70 as immune-related prognostic biomarkers suppress proliferation, migration and invasion of laryngeal cancer cells.

机构信息

Department of Biochemistry, Jinzhou Medical University, Jinzhou, 121000, Liaoning, China.

Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, China.

出版信息

BMC Cancer. 2022 Apr 28;22(1):465. doi: 10.1186/s12885-022-09458-8.

DOI:10.1186/s12885-022-09458-8
PMID:35477402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9047300/
Abstract

BACKGROUND

Laryngeal cancer represents a common malignancy that originates from the larynx, with unfavorable prognosis. Herein, this study systematically analyzed the immune signatures of laryngeal cancer and to evaluate their roles on tumor progression.

METHODS

Differentially expressed immune-related genes (IRGs) were screened between laryngeal cancer and normal tissues from TCGA dataset. Then, two prognosis-related IRGs AQP9 and ZAP70 were analyzed by a series of survival analysis. Based on them, molecular subtypes were constructed by unsupervised cluster analysis. Differences in survival outcomes, HLA expression and immune cell infiltrations were assessed between subtypes. Expression of AQP9 and ZAP70 was validated in laryngeal cancer tissues and cells by RT-qPCR and immunohistochemistry. After silencing and overexpressing AQP9 and ZAP70, CCK-8, EdU, wound healing and transwell assays were performed in TU212 and LCC cells.

RESULTS

Totally, 315 IRGs were abnormally expressed in laryngeal cancer. Among them, AQP9 and ZAP70 were distinctly correlated to patients' prognosis. Two subtypes were developed with distinct survival outcomes, HLA expression and immune microenvironment. Low expression of AQP9 and ZAP70 was confirmed in laryngeal cancer. AQP9 and ZAP70 up-regulation distinctly suppressed proliferation, migration, and invasion of laryngeal cancer cells. The opposite results were investigated when their knockdown.

CONCLUSIONS

Our findings revealed the roles of AQP9 and ZAP70 in progression of laryngeal cancer, and suggested that AQP9 and ZAP70 could potentially act as candidate immunotherapeutic targets for laryngeal cancer.

摘要

背景

喉癌是一种常见的起源于喉部的恶性肿瘤，预后不良。本研究系统分析了喉癌的免疫特征，并评估了它们在肿瘤进展中的作用。

方法

从 TCGA 数据集筛选喉癌与正常组织之间差异表达的免疫相关基因（IRGs）。然后，通过一系列生存分析对两个与预后相关的 IRG AQP9 和 ZAP70 进行分析。在此基础上，通过无监督聚类分析构建分子亚型。评估亚型之间的生存结果、HLA 表达和免疫细胞浸润差异。通过 RT-qPCR 和免疫组织化学验证喉癌组织和细胞中 AQP9 和 ZAP70 的表达。沉默和过表达 AQP9 和 ZAP70 后，在 TU212 和 LCC 细胞中进行 CCK-8、EdU、划痕愈合和 Transwell 实验。

结果

共筛选出 315 个在喉癌中异常表达的 IRGs。其中，AQP9 和 ZAP70 与患者的预后明显相关。两种亚型具有明显不同的生存结果、HLA 表达和免疫微环境。在喉癌中证实 AQP9 和 ZAP70 的表达较低。AQP9 和 ZAP70 的上调明显抑制了喉癌细胞的增殖、迁移和侵袭。当它们被敲低时，得到了相反的结果。

结论

我们的研究结果揭示了 AQP9 和 ZAP70 在喉癌进展中的作用，并表明 AQP9 和 ZAP70 可能是喉癌潜在的免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/03f139015c67/12885_2022_9458_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/bc9d89442993/12885_2022_9458_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/568debdf2c4a/12885_2022_9458_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/c05efaa6a650/12885_2022_9458_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/265c82c02801/12885_2022_9458_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/a7516e2d549a/12885_2022_9458_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/ab2af1cbbc73/12885_2022_9458_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/1d2390c0c691/12885_2022_9458_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/03f139015c67/12885_2022_9458_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/bc9d89442993/12885_2022_9458_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/568debdf2c4a/12885_2022_9458_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/c05efaa6a650/12885_2022_9458_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/265c82c02801/12885_2022_9458_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/a7516e2d549a/12885_2022_9458_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/ab2af1cbbc73/12885_2022_9458_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/1d2390c0c691/12885_2022_9458_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5797/9047300/03f139015c67/12885_2022_9458_Fig8_HTML.jpg

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