Zhu Lei, Hissa Barbara, Győrffy Balázs, Jann Johann-Christoph, Yang Cui, Reissfelder Christoph, Schölch Sebastian
Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary.
Diagnostics (Basel). 2020 May 15;10(5):305. doi: 10.3390/diagnostics10050305.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of death from cancer. Circulating tumor cells (CTCs) with stem-like characteristics lead to distant metastases and thus contribute to the dismal prognosis of PDAC. Our purpose is to investigate the role of stemness in CTCs derived from a genetically engineered mouse model of PDAC and to further explore the potential molecular mechanisms. The publically available RNA sequencing dataset GSE51372 was analyzed, and CTCs with (CTC-S) or without (CTC-N) stem-like features were discriminated based on a principal component analysis (PCA). Differentially expressed genes, weighted gene co-expression network analysis (WGCNA), and further functional enrichment analyses were performed. The prognostic role of the candidate gene () was assessed in a clinical PDAC patient cohort. Overexpression of the pluripotency marker (Krüppel-like factor 4) in CTC-S cells positively correlates with (β-Catenin) expression, and their interaction presumably happens via protein-protein binding in the nucleus. As a result, the adherens junction pathway is significantly enriched in CTC-S. Furthermore, the overexpression of is a negative prognostic factor for progression-free survival (PFS) and relapse-free survival (RFS) in human PDAC cohort. Overexpression of may thus promote the metastatic capabilities of CTCs with stem-like properties via adherens junctions in murine PDAC.
胰腺导管腺癌（PDAC）是癌症死亡的第四大常见原因。具有干细胞样特征的循环肿瘤细胞（CTC）会导致远处转移，从而导致PDAC的预后不良。我们的目的是研究干性在源自PDAC基因工程小鼠模型的CTC中的作用，并进一步探索潜在的分子机制。分析了公开可用的RNA测序数据集GSE51372，并基于主成分分析（PCA）区分具有（CTC-S）或不具有（CTC-N）干细胞样特征的CTC。进行了差异表达基因、加权基因共表达网络分析（WGCNA）以及进一步的功能富集分析。在临床PDAC患者队列中评估了候选基因（）的预后作用。CTC-S细胞中多能性标志物（Krüppel样因子4）的过表达与（β-连环蛋白）表达呈正相关，它们的相互作用可能通过细胞核中的蛋白质-蛋白质结合发生。结果，黏着连接途径在CTC-S中显著富集。此外，在人类PDAC队列中，的过表达是无进展生存期（PFS）和无复发生存期（RFS）的负面预后因素。因此，在小鼠PDAC中，的过表达可能通过黏着连接促进具有干细胞样特性的CTC的转移能力。
