临床肿瘤学杂志

目的 探讨肌酸激酶线粒体1A(CKMT1A)在子宫内膜癌(EC)发生和发展中的作用，并分析其病理生理机制及预后价值。方法 在生物信息学方面，通过GEO2R工具对基因表达综合数据库(GEO)中的微阵列数据集(GSE17025、GSE39099和GSE63678)进行分析，筛选潜在靶基因。从TCGA-UCEC下载转录组数据，分析CKMT1A mRNA表达水平并绘制Kaplan-Meier生存曲线，并对筛选的CKMT1A相关靶基因进行京都基因和基因组百科全书(KEGG)和基因本体论(GO)富集分析。在临床验证部分，回顾性收集2021年9月至2024年6月在徐州医科大学附属连云港医院妇科接受手术的EC患者，共纳入88例EC组织及配对癌旁组织样本。采用免疫组织化学染色法检测CKMT1A蛋白表达，并根据染色程度与强度将患者分为CKMT1A高表达组和CKMT1A低表达组，分析其与术后复发的关系。结果 通过挖掘GEO数据库，将CKMT1A确定为候选基因。TCGA数据分析显示，EC组织中的CKMT1A mRNA表达显著高于正常子宫内膜组织(P=0.005),且高表达与较短的总生存期相关(P<0.001)。GO与KEGG分析提示CKMT1A参与多种代谢过程。临床组织样本中，CKMT1A在EC组织中的高表达率为45.45%,而在癌旁组织中的低表达率为85.23%。与CKMT1A低表达组相比，CKMT1A高表达组患者的临床分期更高(P=0.043),G₃核分级、淋巴血管间隙浸润、深肌层浸润≥1/2及宫颈间质侵犯的比例更高(均P<0.05),且肿瘤直径也更大(P=0.002);此外，CKMT1A高表达组的甘油三酯和血糖水平也较高(P<0.05)。中位随访24.50个月，总复发率为27.27%(24/88)。Cox回归分析结果显示，G₃分级(HR=6.629,P=0.003)、肌层浸润深度≥1/2(HR=10.412,P<0.001)和CKMT1A高表达(HR=9.022,P<0.001)为EC患者复发的预测因素。CKMT1A高表达组的中位无复发生存期短于CKMT1A低表达组(21.38个月vs. 45.16个月，P=0.006)。结论 CKMT1A高表达与EC疾病进展及不良预后密切相关，有望成为EC潜在的生物标志物和治疗靶点，其在EC代谢机制中的作用值得进一步研究。

Objective To analyze the role of amitochondrial creatine kinase 1A(CKMT1A) in the occurrence and development of endometrial cancer(EC), and explore its pathophysiological mechanism and prognostic significance. Methods The microarray datasets(GSE17025, GSE39099, and GSE63678) in the GEO database were analyzed using GEO2R to screen for potential target genes. Transcriptome data was downloaded from TCGA-UCEC to analyze CKMT1A mRNA expression profile and to plot Kaplan-Meier curve. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) pathway annotations were performed on the CKMT1A related target genes identified through screening. In the clinical trial section, from September 2021 to June 2024, a retrospective collection was conducted on EC patients diagnosed and undergoing primary surgery in the Gynecology Department of Lianyungang Hospital Affiliated with Xuzhou Medical University. A total of 88 EC tissue samples and corresponding 88 adjacent tissue samples were obtained. By immunohistochemical staining, the immunoreactivity of CKMT1A was divided into high CKMT1A expression group and low CKMT1A expression group according to the degree and intensity of staining. The prognostic significance of CKMT1A in postoperative recurrence of EC patients was analyzed. Results By mining the GEO database and using P<0.05 and log₂(fold change) as screening criteria, CKMT1A was identified as a candidate gene. Based on TCGA data, the expression of CKMT1A in EC tissue was significantly higher than that in normal endometrial tissue(P=0.005). The higher the expression of CKMT1A, the shorter the overall survival time(P<0.001). GO and KEGG revealed that CKMT1A was involved in numerous metabolic processes. In clinical samples, the high expression rate of CKMT1A was 45.45%, while the low expression rate of CKMT1A in adjacent cancer tissues was 85.23%. Compared with the low CKMT1A expression group, the high CKMT1A expression group had a higher clinical stage(P=0.043), a higher proportion of G₃ nuclear grading, a higher proportion of lymphatic vessel infiltration, a greater proportion of muscle infiltration depth≥1/2, a higher proportion of cervical stromal invasion(all P<0.05), and a larger tumor diameter(P=0.002). In addition, the high CKMT1A expression group had higher levels of triglycerides and blood glucose(P<0.05). The median follow-up period was 24.50 months, with a total recurrence rate of 27.27%(24/88).The Cox regression analysis results revealed that G₃ grading(HR=6.629, P=0.003), muscle infiltration depth≥1/2(HR=10.412, P<0.001), and high CKMT1A expression(HR=9.022, P<0.001) were independent predictive indicators for recurrence in EC patients. In EC cases, patients in the high CKMT1A expression group had a shorter median recurrence free survival compared to those in the low CKMT1A expression group(21.38 months vs. 45.16 months, P=0.006). Conclusion The high expression of CKMT1A is significantly associated with the progression and poor prognosis of EC disease, and is a promising biomarker and therapeutic target for EC. As a candidate target, the metabolic mechanism of CKMT1A in EC deserves further investigation.