目的:细胞周期蛋白依赖性激酶1(CDK1)调节细胞周期,在大多数肿瘤中高表达。CDK1的表达与疾病预后不良有关。本研究旨在确定CDK1在泛癌症中的预后价值,并探讨CDK1表达与免疫细胞浸润之间的关系。
方法:使用在线数据库分析泛癌症中CDK1的表达及其与预后的相关性。通过ESTIMATE和CIBERSORT算法评估免疫浸润。然后,我们评估了CDK1表达与肿瘤突变负荷(TMB)之间的关系,微卫星不稳定性(MSI),或者肿瘤浸润的免疫细胞.此外,我们在泛癌症中进行了免疫相关基因的共表达分析和与CDK1表达的GO分析。最后,我们比较了30对临床胃肠道肿瘤样本中CDK1和免疫相关基因的表达谱.
结果:我们的分析表明CDK1在大多数肿瘤组织中过度表达,尤其是胃肠道肿瘤。CDK1的高表达与总体生存率低有关。疾病特异性生存,无病间隔,肾乳头状细胞癌(KIRP)的无进展间隔,肝细胞癌(LIHC),肺腺癌(LUAD),胰腺腺癌(PAAD),前列腺腺癌(PRAD),和肉瘤(SARC)。此外,CDK1表达与22种癌症类型的TMB和8种癌症类型的MSI以及子宫内膜癌(UCEC)中MSI高(MSI-H)状态和高肿瘤突变负荷(TMB-H)的频率显着相关,胃腺癌(STAD),肉瘤(SARC),直肠腺癌(READ),间皮瘤(MESO),头颈部鳞状细胞癌(HNSC),结肠腺癌(COAD)。此外,CDK1表达与免疫细胞浸润水平相关,如M0、M1或M2巨噬细胞,记忆CD4T细胞,滤泡辅助性T细胞,和幼稚的B细胞。我们的数据显示,在许多癌症类型中,CDK1与47个免疫相关和免疫检查点基因显着相关。此外,CDK1在胃肠道肿瘤样本中上调,尤其是胃癌和肠癌。胃癌组织中CDK1与IDO1、肠癌组织中PD-1呈正相关。
结论:综合来看,我们的数据证明了CDK1在泛癌症的发生和转移中的作用.因此,CDK1是一种潜在的预后生物标志物和肿瘤免疫治疗的靶标。
OBJECTIVE: Cyclin-dependent kinase 1 (
CDK1) regulates the cell cycle and is highly expressed in most tumors.
CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between
CDK1 expression and immune cell infiltration.
METHODS: CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples.
RESULTS: Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer.
CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer.
CONCLUSIONS: Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus,
CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.