Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort.
Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort.
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PBK 在泛癌症队列中的预后、调节和免疫相关作用的组学和药物基因组学证据
DOI：
10.3389/fmolb.2021.785370
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发表时间：
2021
影响因子：
5
通讯作者：
Shen C
中科院分区：
文献类型：
--
作者：
Liu Y;Xiang J;Peng G;Shen C
已知 PDZ 结合激酶 (PBK) 可以调节某些癌症类型的肿瘤进展。然而，其与不同癌症中免疫细胞浸润和预后的关系尚不清楚。本研究通过分析 TCGA、GEO、GETx、TIMER、CPTAC、GEPIA2、cBioPortal、GSCALite、PROGNOSCAN、PharmacoDB、STRING 和 ENCORI 数据库的数据对此进行了调查。 PBK 在大多数肿瘤中过度表达，包括腺皮质癌（风险比 [HR] = 2.178，p < 0.001）、肾肾透明细胞癌（KIRC；HR = 1.907，p < 0.001）、肾肾乳头状细胞癌（HR = 3.024，p < 0.001）和肺腺癌（HR = 1.255，p < 0.001） 0.001），其中与较差的总生存率和晚期病理阶段相关。 PBK 甲基化水平是甲状腺癌 (THCA) 的预后标志物。 32种肿瘤类型中PBK表达量与BIRC5、CCNB1、CDC20、CDK1、DLGAP5、MAD2L1、MELK、PLK1、TOP2A、TTK水平呈正相关；以及转录因子 E2F1 和 MYC 的水平，它们调节细胞凋亡、细胞周期、细胞增殖和侵袭、肿瘤发生和转移。它还受到 microRNA hsa-miR-101-5p、hsa-miR-145-5p 和 hsa-miR-5694 的负调控。 KIRC、肝癌、THCA、胸腺瘤中PBK的表达与B细胞、CD4+T细胞、CD8+T细胞、巨噬细胞、单核细胞、中性粒细胞等免疫细胞的浸润呈正相关。功能富集分析的结果表明，PBK和相关基因通过细胞周期调节促进肿瘤的发生。我们还鉴定了 20 种可能抑制 PBK 表达的药物。因此，PBK 与多种癌症的生存结果相关，并且可能通过增加免疫细胞浸润到肿瘤微环境中来促进肿瘤的发生和进展。这些发现表明 PBK 是一个潜在的治疗靶点，并且在癌症治疗中具有预后价值。
PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.8
作者：
Aksamitiene E;Kholodenko BN;Kolch W;Hoek JB;Kiyatkin A
通讯作者：
Kiyatkin A
影响因子：
5
作者：
Fouad S;Hauton D;D'Angiolella V
通讯作者：
D'Angiolella V
DOI：
10.1073/pnas.090102397
发表时间：
2000-05-09
影响因子：
11.1
作者：
Gaudet, S;Branton, D;Lue, RA
通讯作者：
Lue, RA
影响因子：
8
作者：
Hu, F.;Gartenhaus, R. B.;Rapoport, A. P.
通讯作者：
Rapoport, A. P.