CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.
CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.
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DOI：
10.26502/jbsb.5107060
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zhou, Yu
中科院分区：
文献类型：
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作者：
Zhu, Shikai;Yang, Huining;Liu, Lingling;Jiang, Zhilin;Ji, Juanjuan;Wang, Xiao;Zhong, Lin;Liu, Fulin;Gao, Xueliang;Wang, Haizhen;Zhou, Yu
胰腺导管腺癌（PDAC）是一种高度破坏性的疾病，预后差，发病率不断上升。在这项研究中，我们探讨了CDK 1，CDK 2，CDK 4和CDK 6在早期PDAC进展中的潜在作用。从癌症基因组图谱数据集中获得了140例接受胰腺癌切除术的I/II期PDAC患者的临床病理和mRNA表达数据以及治疗信息。我们的生物信息学分析显示，CDK 1、CDK 2、CDK 4或CDK 6表达水平越高，早期PDAC患者的中位生存期越短。值得注意的是，在低增殖胰腺癌组中，CDKs表达与细胞凋亡、转移、免疫或干性蛋白质功能显著相关。在低增殖的PDAC中，CDK 1的高表达与患者的较短生存期相关，表明CDK 1可能通过细胞周期非依赖性机制调节PDAC的进展。我们的实验数据显示，CDK 1敲低/抑制显著抑制AHR和POU 5 F1的表达水平，这两种关键蛋白在癌细胞转移和干细胞中起作用，在低增殖性胰腺癌细胞中，但在高增殖性胰腺癌细胞中不起作用。总之，我们的研究表明，CDKs不仅通过细胞增殖，而且还通过凋亡，转移，免疫和干性来调节PDAC进展。
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.