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PDZ结合激酶/T-LAK细胞衍生蛋白激酶在人类肿瘤中发挥致癌作用并促进免疫逃逸。

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors.

作者信息

Feng Tingting, Zhang Yan, Ling Sunbin, Xu Chenyang, Lyu Yingqi, Lu Tingting, Liu Xinyuan, Ying Lisha, Wan Yafeng, Zhong Haijun, Su Dan

机构信息

Department of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

Department of Colorectal Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

出版信息

J Oncol. 2021 Sep 23;2021:8892479. doi: 10.1155/2021/8892479. eCollection 2021.

Abstract

BACKGROUND

PDZ binding kinase (PBK)/T-LAK cell-derived protein kinase (TOPK) is an important mitotic kinase that promotes tumor progression in some cancers. However, the pan-cancer analysis of PBK/TOPK and its role in tumor immunity are limited.

METHODS

The oncogenic and immune roles of PBK in various cancers were explored using multiple databases, including Oncomine, Human Protein Atlas, ULCAN, Tumor Immune Estimation Resource 2.0, STRING, and Gene Expression Profiling Interactive Analysis 2, and data collected from The Cancer Genome Atlas and Genotype-Tissue Expression Project. Several bioinformatics tools and methods were used for quantitative analyses and panoramic descriptions, such as the DESeq2 and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm.

RESULTS

PBK was expressed at higher levels in most solid tumors than in normal tissues in multiple databases. PBK was associated with an advanced tumor stage and grade and a poor prognosis in most cases. PBK was associated with tumor immune cell infiltration in most cases and was especially positively correlated with TAMs, Tregs, MDSCs, and T cell exhaustion in KIRC, LGG, and LIHC. PBK was closely related to TMB, MSI, and immune checkpoint genes in various cancers, and patients with higher expression of PBK in KIRC, LGG, and LIHC had higher TIDE scores and lower immune responses in the predicted results. PBK was closely related to cell cycle regulation and immune-related processes in LIHC and LGG according to GO and KEGG enrichment analyses.

CONCLUSIONS

PBK may play an oncogenic role in most solid tumors and promotes immune escape, especially in KIRC, LGG, and LIHC. This study suggests the potential value of PBK inhibitors combined with immunotherapy.

摘要

背景

PDZ结合激酶(PBK)/T淋巴细胞激活的杀伤细胞衍生蛋白激酶(TOPK)是一种重要的有丝分裂激酶,在某些癌症中促进肿瘤进展。然而,PBK/TOPK的泛癌分析及其在肿瘤免疫中的作用有限。

方法

利用多个数据库,包括Oncomine、人类蛋白质图谱、ULCAN、肿瘤免疫评估资源2.0、STRING和基因表达谱交互分析2,以及从癌症基因组图谱和基因型-组织表达项目收集的数据,探索PBK在各种癌症中的致癌和免疫作用。使用了几种生物信息学工具和方法进行定量分析和全景描述,如DESeq2和肿瘤免疫功能障碍与排除(TIDE)算法。

结果

在多个数据库中,大多数实体瘤中PBK的表达水平高于正常组织。在大多数情况下,PBK与肿瘤晚期、高级别以及不良预后相关。在大多数情况下,PBK与肿瘤免疫细胞浸润相关,在肾透明细胞癌(KIRC)、低级别胶质瘤(LGG)和肝细胞癌(LIHC)中尤其与肿瘤相关巨噬细胞(TAM)、调节性T细胞(Treg)、髓源性抑制细胞(MDSC)和T细胞耗竭呈正相关。PBK在各种癌症中与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)和免疫检查点基因密切相关,在KIRC、LGG和LIHC中PBK表达较高的患者在预测结果中具有较高的TIDE评分和较低的免疫反应。根据基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,PBK在LIHC和LGG中与细胞周期调控和免疫相关过程密切相关。

结论

PBK可能在大多数实体瘤中发挥致癌作用并促进免疫逃逸,尤其是在KIRC、LGG和LIHC中。本研究提示了PBK抑制剂联合免疫治疗的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a14/8486520/15b50a77eb3c/JO2021-8892479.001.jpg

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