ANXA2、FOLR1、ENO1在宫颈癌中的表达与放疗敏感性及预后的关系

Association of ANXA2,FOLR1,and ENO1 expression with radiotherapy sensitivity and prognosis in cervical cancer

摘要

目的 探讨膜联蛋白 A2(ANXA2)、叶酸受体1(FOLR1)、烯醇化酶-1(ENO1)在宫颈癌中的表达与放疗敏感性及预后的关系。方法 选取2018年1月至2020年1月本院120例宫颈癌初诊患者为研究对象。收集癌组织及相应的癌旁组织,采用免疫组织化学法检测组织中 ANXA2、FOLR1、ENO1表达情况。放疗4周后,根据放疗结果将患者分为放疗敏感组(n=69)和放疗抵抗组(n=51),比较两组 ANXA2、FOLR1、ENO1表达及临床病理特征;多因素 Logistic回归分析影响放疗敏感性的因素;生存曲线分析 ANXA2、FOLR1、ENO1表达对宫颈癌患者预后生存率的影响。结果 放疗抵抗组 ANXA2、FOLR1、ENO1的阳性率明显高于放疗敏感组、癌旁组(t=47.270、36.938、49.406,P <0.05);放疗敏感组和放疗抵抗组不同国际妇产科联盟(FIGO)分期、分化程度、宫颈浸润深度患者比例比较,差异具有统计学意义(χ² =4.561、7.103、5.035,P <0.05);分化程度(HR=1.398,95%CI:1.067~1.832)、宫颈浸润深度(HR =1.654,95%CI:1.046~2.616)、ANXA2(HR =2.881,95%CI:1.265~6.562)、FOLR1(HR=1.324,95%CI:1.036~1.692)、ENO1(HR=1.726,95%CI:1.192~2.450)表达为放疗敏感性的影响因素(P<0.05);与 ANXA2、FOLR1、ENO1阴性表达患者相比,ANXA2、FOLR1、ENO1阳性表达患者3年生存率明显降低(61.54% vs. 87.27%,59.38% vs. 89.29%,63.49% vs. 84.21%,χ²=11.151、13.932、7.510,P<0.05)。结论 宫颈癌组织 ANXA2、FOLR1、ENO1阳性表达与患者放疗抵抗、生存率降低密切相关。

Abstract

Objective To investigate the relationship between annexin A2 (ANXA2),folate receptor 1 (FOLR1),and enolase-1 (ENO1) expression in cervical cancer and radiotherapy sensitivity and prognosis. Methods From January 2018 to January 2020,120 patients with new cervical cancer treated in our hospital were included as the study subjects.Cancer tissues and corresponding adjacent tissues were collected,and immunohistochemistry was used to detect the expression of ANXA2,FOLR1,and ENO1 in the tissues.After 4 weeks of radiotherapy,patients were assigned into radiotherapy-sensitive group (n=69) and radiotherapy-resistant group (n=51) based on the radiotherapy results.The expression of ANXA2,FOLR1,ENO1,and clinicopathological characteristics were compared between the two groups.Multivariate logistic regression was used to analyze the factors affecting radiotherapy sensitivity.Kaplan-Meier curves were plotted to analyze the impacts of ANXA2,FOLR1,and ENO1 expression on the prognostic survival rate of cervical cancer patients. Results The positive rates of ANXA2,FOLR1,and ENO1 in the radiotherapy resistant group were significantly higher than those in the radiotherapy sensitive group and the adjacent tissue group ( t=47.270,36.938,49.406,P<0.05).The differences in different FIGO stages,differentiation degrees,and cervical infiltration depths between the radiotherapy sensitive group and the radiotherapy resistant group were statistically significant (χ² =4.561,7.103,5.035,P <0.05).The differentiation degree (HR=1.398,95%CI:1.067-1.832),cervical infiltration depth (HR=1.654,95%CI:1.046-2.616),ANXA2 (HR=2.881,95%CI:1.265-6.562),FOLR1 (HR=1.324,95%CI:1.036-1.692),and ENO1 (HR=1.726,95%CI:1.192-2.450) expression were factors influencing radiotherapy sensitivity (P<0.05).Patients with positive expression of ANXA2,FOLR1,and ENO1 had significantly lower 3-year survival rates compared with patients with negative expression of ANXA2,FOLR1,and ENO1 (61.54% vs.87.27%,59.38% vs.89.29%,and 63.49% vs.84.21%,χ ²=11.151,13.932,7.510,P<0.05). Conclusion The positive expression of ANXA2,FOLR1,and ENO1 in cervical cancer tissues is closely related to radiotherapy resistance and reduced survival rates.

关键词

宫颈癌 / 膜联蛋白 A2 / 叶酸受体1 / 烯醇化酶-1 / 放疗敏感性 / 预后

Key words

cervical cancer / annexin A2 / folate receptor 1 / enolase-1 / radiotherapy sensitivity / prognosis

参考文献

[1] 田文, 尹晓梅, 付淼, 等. MYLIP和 miR-542-3p与宫颈癌患者早期诊断及临床预后的关系[J]. 中国妇幼健康研究, 2024, 35(10): 55-62.

[2] Lindegaard J C, Petric P, Tan L T, et al. Are we making progress in curing advanced cervical cancer-again[J]. Int J Gynecol Cancer, 2024, 34(12): 1940-1945.

[3] Song L, Gao Y, Wang Z, et al. Serum levels of intercellular adhesion molecule 1 and vascular Cell adhesion molecule 1 as biomarkers to predict radiotherapy sensitivity in cervical cancer[J]. Geburtshilfe Frauenheilkd, 2024, 84(4): 370-377.

[4] Huang L, Xu K, Yang Q, et al. ANXA2 in cancer:aberrant regulation of tumour cell apoptosis and its immune interactions[J]. Cell Death Discov, 2025, 11(1): 174-187.

[5] Chen C I, Li W S, Chen H P, et al. High expression of folate receptor alpha (FOLR1) is associated with aggressive tumor behavior,poor response to chemoradiotherapy,and worse survival in rectal cancer[J]. Technol Cancer Res Treat, 2022, 21(1): 1-7.

[6] Ma Q, Jiang H, Ma L, et al. The moonlighting function of glycolytic enzyme enolase-1 promotes choline phospholipid metabolism and tumor cell proliferation[J]. Proc Natl Acad Sci U S A, 2023, 120(15): e2209435120.

[7] 赵挺祺, 李时荣, 王静媛, 等. 非小细胞肺癌中 LASS2/TMSG1的表达及其临床意义[J]. 临床与实验病理学杂志, 2020, 36(3): 323-325.

[8] Tsuchida Y, Therasse P. Rsponse evaluation criteria in solid tumors(RECIST):new guidelines[J]. Med Pediatr Oncol, 2001, 37(1): 1-3.

[9] 王静, 易宣洪, 汪萍, 等. CircYPEL2通过 miR-498/MSMO1轴调节宫颈癌细胞的放射敏感性[J]. 中国妇幼健康研究, 2023, 34(10): 60-69.

[10] Yang J, Cai H, Xiao Z X, et al. Effect of radiotherapy on the survival of cervical cancer patients:an analysis based on SEER database. Medicine (Baltimore)[J]. 2019, 98(30): e16421.

[11] 顾尚尉, 艾丛慧, 王关顺, 等. MRI及影像组学在宫颈癌放化疗疗效及预后评估中的研究进展[J]. 放射学实践, 2024, 39(5): 699-703.

[12] Jääskeläinen E, Kärkkäinen H, Palmgren J E, et al. Implementing treatment according to the guidelines is of paramount importance in locally advanced cervical cancer:a real-world study[J]. Front Oncol, 2025, 15(1): 1562067.

[13] Jiao X, Zhang S, Jiao J, et al. Promoter methylation of SEPT9 as a potential biomarker for early detection of cervical cancer and its overexpression predicts radioresistance[J]. Clin Epigenetics, 2019, 11(1): 120-133.

[14] Ning Y, Li Y, Wang H. ANXA2 is a potential biomarker for cancer prognosis and immune infiltration:a systematic pan-cancer analysis[J]. Front Genet, 2023, 14(1): 1108167.

[15] Buttarelli M, Babini G, Raspaglio G, et al. A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer[J]. J Exp Clin Cancer Res, 2019, 38(1): 279-295.

[16] Wang R, Zhang Y. RecQ protein-like 4 drives cisplatin chemosensitivity of cervical cancer cells by modulating annexin A2[J]. Drug Dev Res, 2024, 85(7): e70003.

[17] Ma K, Chen X, Liu W, et al. ANXA2 is correlated with the molecular features and clinical prognosis of glioma,and acts as a potential marker of immunosuppression[J]. Sci Rep, 2021, 11(1): 20839-20852.

[18] Ge Y, Wang B, Xiao J, et al. NUSAP1 promotes gastric cancer radioresistance by inhibiting ubiquitination of ANXA2 and is suppressed by miR-129-5p[J]. J Cancer Res Clin Oncol, 2024 Aug 30; 150(8): 406-421.

[19] Nawaz F Z, Kipreos E T. Emerging roles for folate receptor FOLR1 in signaling and cancer[J]. Trends Endocrinol Metab, 2022, 33(3): 159-174.

[20] Hu C, Liu T, Han C, et al. HPV E6/E7 promotes aerobic glycolysis in cervical cancer by regulating IGF2BP2 to stabilize mA-MYC expression[J]. Int J Biol Sci, 2022, 18(2): 507-521.

[21] Zhang X, Zhang Y, Liu Q, et al. Glycolysis-associated lncRNAs in cancer energy metabolism and immune microenvironment:a magic key[J]. Front Immunol, 2024, 15(1): 1456636.

[22] Li Y, Liu L, Li B. Role of ENO1 and its targeted therapy in tumors[J]. J Transl Med, 2024, 22(1): 1025-1041.

[23] 丁世凯, 张正华, 张秀莉. 降低有氧糖酵解增强非小细胞肺癌耐药细胞对顺铂的敏感性 [J]. 现代肿瘤医学, 2024, 32(11): 1973-1977.

[24] 马建红, 高亚婷, 万子华, 等. 糖代谢与宫颈癌关系及其致病机制的研究进展[J]. 国际妇产科学杂志, 2023, 50(3): 275-280.

[25] 陈霄, 吴小颖, 安明. 宫颈癌组织中 NEK2和circPITX1的表达水平与放疗敏感度及预后的相关性研究[J]. 现代检验医学杂志, 2023, 38(1): 27-32.

基金资助

河北省2021年度医学科学研究课题计划(20210127)