肿瘤诊治与预后专栏

子宫内膜癌患者血浆CCNE1IRX2XPR1基因甲基化与临床病理特征及预后的关联性

  • 梁怀枫 ,
  • 李思瑾 ,
  • 李道成
展开
  • 广州中医药大学第一附属医院妇儿中心三妇科 (广东 广州 510000 )

收稿日期: 2026-03-23

  网络出版日期: 2026-08-05

基金资助

广东省医学科学技术研究基金项目(B2024039)

Correlation analysis of methylation levels of plasma CCNE1IRX2, and XPR1 genes with clinicopathological features and prognosis in patients with endometrial cancer

  • Huaifeng LIANG ,
  • Sijin LI ,
  • Daocheng LI
Expand
  • Department of Gynecology,Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong,China

Received date: 2026-03-23

  Online published: 2026-08-05

摘要

目的 探讨子宫内膜癌(EC)患者血浆细胞周期蛋白E1(CCNE1)、易洛魁人同源框2(IRX2)、异嗜性和多嗜性逆转录病毒受体1(XPR1)基因甲基化与临床病理特征及预后的关联性。 方法 选取2018年6月至2022年12月在医院进行手术治疗的EC患者120例(观察组),根据患者预后分为生存组(88例)、死亡组(32例)。另选取年龄相匹配的100例健康志愿者作为对照组。甲基化特异性实时定量聚合酶链反应检测血浆CCNE1IRX2XPR1基因甲基化水平;Kaplan-Meier法分析血浆CCNE1IRX2XPR1甲基化水平与EC患者预后的关系;Cox风险回归模型分析EC患者预后影响因素;受试者工作特征(ROC)曲线评估血浆CCNE1IRX2XPR1甲基化对EC患者预后不良的预测价值。 结果 相较于对照组,观察组血浆CCNE1XPR1甲基化水平降低,IRX2甲基化水平升高(P < 0.05)。FIGO分期Ⅲ + Ⅳ期、组织学分级低分化、浸润肌壁深度 ≥ 1/2肌层、有淋巴结转移患者CCNE1XPR1甲基化呈低表达,IRX2甲基化呈高表达(P < 0.05)。120例EC患者共随访5 ~ 36个月,中位随访时间为21个月,其中32例患者死亡,3年总生存率为73.33%(88/120)。血浆CCNE1XPR1甲基化低表达患者3年总生存率低于其高表达组(χ2 = 4.729、6.136,P = 0.030、0.013),血浆IRX2甲基化高表达患者3年总生存率低于其低表达组(χ2 = 6.569,P = 0.010)。相较于生存组,死亡组CCNE1XPR1甲基化水平降低,IRX2甲基化水平升高(P < 0.05)。IRX2高甲基化是EC患者预后不良的危险因素,CCNE1高甲基化、XPR1高甲基化则是保护因素(P < 0.05)。血浆CCNE1IRX2XPR1甲基化单独预测EC患者预后不良的AUC = 0.827、0.820、0.816,三者联合预测的AUC = 0.941,联合预测效能较优(Z = 3.427、2.610、3.068,P = 0.001、0.009、0.002)。 结论 EC患者血浆CCNE1XPR1甲基化水平降低,IRX2甲基化水平升高,均与临床病理特征、预后不良密切相关,三者联合对EC患者预后不良具有较高的预测价值。

本文引用格式

梁怀枫 , 李思瑾 , 李道成 . 子宫内膜癌患者血浆CCNE1IRX2XPR1基因甲基化与临床病理特征及预后的关联性[J]. 实用医学杂志, 2026 , 42(14) : 2550 -2557 . DOI: 10.3969/j.issn.1006-5725.2026.14.008

Abstract

Objective To investigate the association between the methylation levels of plasma cyclin E1 (CCNE1), iroquois homeobox protein 2 (IRX2), and xenotropic and polytropic retrovirus receptor 1 (XPR1) genes, and the clinicopathological features and prognosis in patients with endometrial cancer (EC). Methods A total of 120 patients with EC who underwent surgical treatment at the hospital between June 2018 and December 2022 (study group) were selected and divided into the survival group (88 cases) and the death group (32 cases) based on the patients' prognosis. Another 100 healthy volunteers of matching age were recruited as the control group. The methylation levels of plasma CCNE1IRX2, and XPR1 genes were detected using methylation-specific real-time quantitative polymerase chain reaction. The relationship between the methylation levels of plasma CCNE1IRX2, and XPR1 and the prognosis of EC patients was analyzed by the Kaplan-Meier method. The Cox risk regression model was employed to analyze the prognostic factors of EC patients. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value of plasma CCNE1IRX2, and XPR1 methylation for poor prognosis in patients with endometrial cancer. Results Compared with the control group, the methylation levels of plasma CCNE1 and XPR1 in the study group were lower, whereas the methylation level of IRX2 was higher (P < 0.05). In patients with FIGO stage Ⅲ + Ⅳ, poorly differentiated histological grade, myometrial infiltration depth ≥ 1/2 myometrium, and lymph node metastasis, the methylation levels of CCNE1 and XPR1 were low, while the methylation level of IRX2 was high (P < 0.05). A total of 120 EC patients were followed up for 5 - 36 months, with a median follow-up time of 21 months. Among them, 32 patients died, and the 3-year overall survival rate was 73.33% (88/120). The 3-year overall survival rate of patients with low expression of plasma CCNE1 and XPR1 methylations was lower than that of the high-expression groups (χ2 = 4.729, 6.136; P = 0.030, 0.013), and the 3-year overall survival rate of patients with high expression of plasma IRX2 methylation was lower than that of the low-expression groups (χ2 = 6.569; P = 0.010). Compared with the survival group, the methylation levels of CCNE1 and XPR1 in the death group were lower, and the methylation level of IRX2 was higher (P < 0.05). Hypermethylation of IRX2 was a risk factor for poor prognosis in patients with EC, while hypermethylation of CCNE1 and hypermethylation of XPR1 were protective factors (P < 0.05). The AUC values for plasma CCNE1IRX2, and XPR1 methylation as individual predictors of poor prognosis in EC patients were 0.827, 0.820, and 0.816, respectively; The AUC for the combined prediction was 0.941, indicating superior predictive performance (Z = 3.427, 2.610, 3.068; P = 0.001, 0.009, 0.002). Conclusions Reduced levels of CCNE1 and XPR1 methylation, along with elevated levels of IRX2 methylation, in the plasma of endometrial cancer patients are closely associated with clinical and pathological characteristics as well as poor prognosis. The combination of these three markers holds high predictive value for poor prognosis in endometrial cancer patients.

参考文献

[1] HABESHIAN T S, PARK S Y, CONTI D, et al. Inflammatory and insulinemic dietary and lifestyle patterns and incidence of endometrial cancer: The multiethnic cohort[J]. Am J Clin Nutr, 2025, 121(6):1236-1245. doi: 10.1016/j.ajcnut. 2025.04. 020 .
[2] CONCIN N, MATIAS-GUIU X, CIBULA D, et al. ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: Update 2025[J]. Lancet Oncol, 2025, 26(8):423-435. doi: 10.1016/S1470-2045(25)00167-6 .
[3] 刘露, 丁慧静, 张坤. 子宫内膜癌早期筛查和诊断技术的研究进展[J]. 中国性科学, 2026, 35(3):35-38. doi: 10.3969/j.issn.1672-1993.2026.03.008 .
[4] NISHIKUBO H, KAWABATA K, SANO T, et al. CCNE1 gene amplification might be associated with lymph node metastasis of gastric cancer[J]. Genes (Basel), 2025, 16(6):617. doi: 10.3390/genes16060617 .
[5] ZHENG X, CHEN L, LIU W, et al. CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: A pan-cancer analysis[J]. Hereditas, 2023, 160(1):13. doi: 10.1186/s41065-023-00273-0 .
[6] MA Z G, YUAN Y P, FAN D, et al. IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice[J]. Nat Commun, 2023, 14(1):4967. doi: 10.1038/s41467-023-40639-6 .
[7] XU Q, ZHOU W, ZHOU Y, et al. IRX2 regulates endometrial carcinoma oncogenesis by transcriptional repressing RUVBL1[J]. Exp Cell Res, 2024, 434(1):113866. doi: 10.1016/j.yexcr. 2023.113866 .
[8] HAN X, YANG L, NUERMANGULI R, et al. In-depth evaluation of XPR1 as a new prognostic indicator for endometrial cancer[J]. BMC Cancer, 2025, 25(1):1411. doi: 10.1186/s12885-025-14818-1 .
[9] COLOMBO N, CREUTZBERG C, AMANT F, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, treatment and follow-up[J]. Ann Oncol, 2016, 27(1):16-41. doi: 10.1097/IGC.0000000000000609 .
[10] 翟一阳, 马韵翼, 翟俊英, 等. 子宫内膜癌组织肿瘤坏死因子α诱导蛋白8家族成员2、细胞增殖核抗原表达水平及与临床病理参数和预后的关系[J]. 实用医学杂志, 2025, 41(3):379-384. doi: 10.3969/j.issn.1006-5725.2025.03.011 .
[11] GAO S, WANG J, LI Z, et al. Global Trends in incidence and mortality rates of endometrial cancer among individuals aged 55 years and above from 1990 to 2021: An Analysis of the Global Burden of Disease[J]. Int J Womens Health, 2025, 17(1):651-662. doi: 10.2147/IJWH.S499435 .
[12] GODDARD E, PACE D, TWELLS L, et al. Laparoscopic bariatric surgery with hysterectomy for endometrial cancer to improve long-term outcomes: A review article[J]. Int J Gynecol Cancer, 2025, 35(2):100033. doi: 10.1016/j.ijgc.2024.100033 .
[13] 中国医师协会微无创医学专业委员会妇科肿瘤学组, 中国医院协会妇产医院分会妇科肿瘤专业学组, 中国优生科学协会肿瘤生殖学分会, 等. 子宫内膜未分化/去分化癌诊治的中国专家共识(2022年版)[J]. 癌症进展, 2023, 21(1):1-9, 14. doi: 10.11877/j.issn.1672-1535.2023.21.01.01 .
[14] XU T, DING H, CHEN J, et al. Research progress of DNA Methylation in Endometrial cancer[J]. Biomolecules, 2022, 12(7):938. doi: 10.3390/biom12070938 .
[15] TAKAMATSU S, HILLMAN R T, YOSHIHARA K, et al. Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study[J]. Br J Cancer, 2024, 131(8): 1340-1349. doi: 10.1038/s41416-024-02837-x .
[16] ULLAH M A, FARZANA M, ISLAM M S, et al. Identification of the prognostic and therapeutic values of cyclin E1 (CCNE1) gene expression in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: A database mining approach[J]. Heliyon, 2022, 8(9):10367. doi: 10.1016/j.heliyon.2022.e10367 .
[17] LABEAU T, LOGER J S, JEAN-LAURENT M, et al. Molecular profiling of endometrial cancer in martinique reveals frequent CCNE1 amplification in poor prognosis tumors[J]. Sci Rep, 2025, 15(1):40830. doi: 10.1038/s41598-025-24580-w .
[18] MARLIN R, LOGER J S, JOACHIM C, et al. Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis[J]. Cell Oncol (Dordr), 2024, 47(4):1441-1457. doi: 10.1007/s13402-024-00942-w .
[19] CATELA C, ASSIMACOPOULOS S, CHEN Y, et al. The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development[J]. iScience, 2025, 28(4):112210. doi: 10.1016/j.isci.2025.112210 .
[20] ZHANG J, ZHOU Y, LI X, et al. Expression profile and prognostic values of irx family members in lung adenocarcinoma[J]. Curr Med Chem, 2025, 32(35): 7906-7924. doi: 10.2174/0109298673320965240829065919 .
[21] HUANG J, YUAN L, HUANG W, et al. LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response[J]. Front Immunol, 2022, 13(1):1064874. doi: 10.3389/fimmu.2022.1064874 .
[22] ZHANG X Y, LIU Y, RONG Q, et al. RUVBL1 accelerates tongue squamous cell carcinoma by mediating CRaf/MEK/ERK pathway[J]. iScience, 2024, 27(4):109434. doi: 10.1016/j.isci.2024.109434 .
[23] SU Y, MEI L, WU Y, et al. Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway[J]. J Endocrinol Invest, 2025, 48(3):633-652. doi: 10.1007/s40618-024-02481-5 .
[24] SUN C, GUAN H, LI J, et al. RBM15-mediated m6A modification of XPR1 promotes the malignant progression of lung adenocarcinoma[J]. Naunyn Schmiedebergs Arch Pharmacol, 2025, 398(7):9279-9290. doi: 10.1007/s00210-025- 03849-x .
[25] WANG L. Bioinformatics analyses proposed xenotropic and polytropic retrovirus receptor 1 as a potential diagnostic and prognostic biomarker and immunotherapeutic target in head and neck squamous cell carcinoma[J]. Auris Nasus Larynx, 2023, 50(1):134-150. doi: 10.1016/j.anl.2022.05.018 .
[26] AKASU-NAGAYOSHI Y, HAYASHI T, KAWABATA A, et al. PHOSPHATE exporter XPR1/SLC53A1 is required for the tumorigenicity of epithelial ovarian cancer[J]. Cancer Sci, 2022, 113(6):2034-2043. doi: 10.1111/cas.15358 .
文章导航

/