Relationship between CKMT1A as a metabolic marker and the prognosis of endometrial cancer

ZHANG Jingwen; FENG Wen; WANG Xiaoyu

doi:10.3969/j.issn.1009-0460.2025.08.008

Abstract：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.