CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma

Author(s): Shikai Zhu, Huining Yang, Lingling Liu, Zhilin Jiang, Juanjuan Ji, Xiao Wang, Lin Zhong, Fulin Liu, Xueliang Gao, Haizhen Wang and Yu Zhou

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 cycleindependent 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.