Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska University Hospital, Solna, 27106Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, 27106Karolinska Institutet, Stockholm, Sweden.
Cancer Control. 2022 Jan-Dec;29:10732748221094797. doi: 10.1177/10732748221094797.
Several markers of survival among endometrial cancer (EC) patients have been proposed, namely, the oncoprotein stathmin, RAF kinase inhibitor (RKIP), Cyclin A, GATA-binding protein 3 (GATA3), and growth and differentiation factor-15 (GDF-15). Their elevated expression correlated significantly with a high stage, serous papillary/clear cell subtypes, and aneuploidy. In a previous study, we reported the elevated expression of the serine/threonine protein kinase N1 (PKN1) in cancerous cells. In the present paper, we studied PKN1 expression in EC tissues from a large cohort of patients, to determine whether PKN1 can serve as a marker for the aggressiveness and prognosis of EC, and/or as a marker of survival among EC patients.
Tissue samples from EC patients were examined retrospectively for tumor type, tumor size, FIGO stage and grade, depth of invasion in the myometrium, and presence of lymph node metastasis. The PKN1 protein expression in EC cells was assessed by immunohistochemistry. mRNA levels were analyzed in publicly available databases, using bioinformatic tools.
We found that expression of at the mRNA and proteins levels tended to increase in high-grade EC samples (P = .0001 and P = .06, respectively). In addition, patients with metastatic disease had higher PKN1 mRNA levels (P = .02). Moreover, patients with high expression could be characterized by poorer survival.
We have shown a trend of the higher expression levels in EC patients with poor prognosis. Therefore, might be considered as a candidate prognostic marker for EC.
已经提出了几种子宫内膜癌 (EC) 患者的生存标志物，即癌蛋白 stathmin、RAF 激酶抑制剂 (RKIP)、细胞周期蛋白 A、GATA 结合蛋白 3 (GATA3) 和生长分化因子 15 (GDF-15)。它们的高表达与高分期、浆液性乳头状/透明细胞亚型和非整倍体显著相关。在之前的一项研究中，我们报告了丝氨酸/苏氨酸蛋白激酶 N1 (PKN1) 在癌细胞中的表达升高。在本研究中，我们研究了来自大量患者的 EC 组织中的 PKN1 表达，以确定 PKN1 是否可以作为 EC 侵袭性和预后的标志物，以及/或作为 EC 患者生存的标志物。
回顾性检查 EC 患者的组织样本，以确定肿瘤类型、肿瘤大小、FIGO 分期和分级、子宫肌层浸润深度以及淋巴结转移情况。通过免疫组织化学评估 EC 细胞中的 PKN1 蛋白表达。使用生物信息学工具在公开可用的数据库中分析 mRNA 水平。
我们发现，在高级别 EC 样本中，mRNA 和蛋白质水平的表达均有升高的趋势（P =.0001 和 P =.06）。此外，患有转移性疾病的患者具有更高的 PKN1 mRNA 水平（P =.02）。此外，具有高 表达的患者的生存较差。
我们已经显示出 EC 患者预后不良的 表达水平升高的趋势。因此， 可能被认为是 EC 的候选预后标志物。
