Abstract:Objective: To explore the relationship between the expression of Prospero-related homeobox protein 1 (PROX1) and Krüppel-like factor 4 (KLF4) in breast cancer patients and their relation with disease progression and prognosis. Methods: A total of 257 patients with breast cancer admitted to our hospital from May 2019 to April 2022 were selected as the breast cancer group, and another 257 patients with benign breast lesions were selected as the benign breast lesion group. The levels of serum PROX1 and KLF4 were measured using enzyme-linked immunosorbent assay (ELISA). The levels of serum PROX1 and KLF4 were compared between the two groups, as well as among patients with different pathological characteristics of breast cancer. The relationship between the levels of serum PROX1 and KLF4 and the prognostic survival of breast cancer patients was analyzed. COX regression analysis was used to investigate the factors affecting the prognostic survival of breast cancer patients and the relationship between the levels of serum PROX1 and KLF4 and the prognostic survival of various subgroups. The restricted cubic spline (RCS) model was used to analyze the nonlinear relationship between the levels of serum PROX1 and KLF4 and the prognostic survival of breast cancer patients. Results: The serum PROX1 level in breast cancer patients was higher than that in patients with benign breast lesions, while the KLF4 level was lower than that in patients with benign breast lesions (P<0.05). The serum PROX1 and KLF4 levels in breast cancer patients showed significant differences in the differentiation degree, clinical stage, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (Her-2), molecular typing, and lymph node metastasis (P<0.05). Among 257 breast cancer patients followed up for 24 months, seven were lost to follow-up, yielding a survival rate of 77.20% (193/250). The survival rate of patients with high PROX1 levels at 24 months was 65.93%, significantly lower than that of patients with low PROX1 levels at 90.43%. The survival rate of patients with high KLF4 levels at 24 months was 87.80%, significantly higher than that of patients with low KLF4 levels at 66.93% (P<0.05). Multivariate COX regression analysis showed that differentiation degree, clinical stage, lymph node metastasis, and serum PROX1 and KLF4 levels were independent factors affecting the prognosis and survival of breast cancer patients (P<0.05). Subgroup analysis indicated a significant interaction between serum PROX1 and KLF4 levels and clinical stage and lymph node metastasis in terms of prognosis and survival in breast cancer patients. In the RCS model, the serum PROX1 and KLF4 levels in breast cancer patients showed a linear relationship with the risk of death (P<0.05). Conclusion: Patients with breast cancer have elevated serum levels of PROX1 and decreased levels of KLF4, which is closely related to the progression and prognosis of breast cancer. Monitoring the levels of serum PROX1 and KLF4 in breast cancer patients may help to identify the risk of breast cancer and death in the early stage and improve the prognosis of patients.
闫沙沙, 高小丽, 栾艳超, 韩青松. 乳腺癌患者PROX1 KLF4水平及与病情进展预后的关系[J]. 河北医学, 2026, 32(2): 259-265.
YAN Shasha, GAO Xiaoli, LUAN Yanchao, et al. Levels of PROX1 and KLF4 in Breast Cancer Patients and Their Relationship with Disease Progression and Prognosis. HeBei Med, 2026, 32(2): 259-265.
[1] 张红美,胡丽丽,李平,等.青年乳腺癌与中老年乳腺癌患者临床及病理特征比较[J].临床误诊误治,2024,37(15):41-44. [2] Roy M,Fowler AM,Ulaner GA,et al.Molecular classification of breast cancer[J].PET Clin,2023,18(4):441-458. [3] Zhu LZ,Tian Q,Gao H,et al.PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK[J].Int Biol Sci,2022,18(5):2032-2046. [4] Wang RZ,Yu WD,Zhu TH,et al.MED27 plays a tumor-promoting role in breast cancer progression by targeting KLF4[J].Cancer Sci,2023,114(6):2277-2292. [5] Will M,Liang J,Metcalfe C,et al.Therapeutic resistance to anti-oestrogen therapy in breast cancer[J].Nat Rev Cancer,2023,23(10):673-685. [6] Michail A,Gkikas D,Stellas D,et al.Prox1 suppresses the proliferation of breast cancer cells via direct inhibition of c-Myc gene expression[J].Cells,2023,12(14):1869-1874. [7] Gan L,Li QG,Nie W,et al.PROX1-mediated epigenetic silencing of SIRT3 contributes to proliferation and glucose metabolism in colorectal cancer[J].Int Biol Sci,2023,19(1):50-65. [8] 王树江,张明,刘鹏.乳腺癌组织中miR-181、Prox1的表达及临床意义[J].中国中西医结合外科杂志,2020,26(2):254-258. [9] 李海丽,张丰,郑吉春,等.碱性成纤维细胞生长因子、PROX1在乳腺癌组织中表达及其与预后的关系[J].中国医刊,2023,58(1):100-104. [10] Morales-Martinez M,Vega GG,Neri N,et al.MicroRNA-7 regulates migration and chemoresistance in non-hodgkin lymphoma cells through regulation of KLF4 and YY1[J].Front Oncol,2020,10(4):5888-5893. [11] Ganguly K,Krishn SR,Rachagani S,et al.Secretory mucin 5AC promotes neoplastic progression by augmenting KLF4-mediated pancreatic cancer cell stemness[J].Cancer Res,2021,81(1):91-102. [12] Zhu KY,Tian Y,Li YX,et al.The functions and prognostic value of Kruppel-like factors in breast cancer[J].Cancer Cell Int,2022,22(1):23-27. [13] 张文涛,董汉华,赵亚鹏,等.超声造影及TgAb、SP1和KLF4表达水平对分化型甲状腺癌临床分期的诊断价值[J].实用癌症杂志,2024,39(5):701-704,709. [14] 黄胜超,邱璞,陈英毓,等.真核细胞起始因子4E和Krüppel样因子4在乳腺癌的表达及其临床意义[J].中华实验外科杂志,2021,38(4):623-625.