三阴性乳腺癌组织中ZNF545表达与预后及腋窝淋巴结转移的关系-现代医学

三阴性乳腺癌组织中ZNF545表达与预后及腋窝淋巴结转移的关系

单位：唐山市人民医院乳腺外一科, 河北唐山 063001

分类号：R392.3

出版年·卷·期（页码）：2023·51·第四期（462-468）

摘要：

目的:探讨三阴性乳腺癌组织锌指蛋白545(ZNF545)的表达与预后及腋窝淋巴结转移的关系。方法:采用免疫组织化学染色法检测107例三阴性乳腺癌患者癌组织中ZNF545、Wnt/β-catenin信号通路相关蛋白(β-catenin 和C-myc)表达水平。采用Logistic多因素分析影响三阴性乳腺癌患者腋窝淋巴结转移的影响因素。Kaplan-Meier法用于三阴性乳腺癌患者预后的单因素分析，Cox比例风险回归模型用于三阴性乳腺癌患者预后的多因素分析。结果:三阴性乳腺癌组织中 ZNF545低表达者50例(46.7%)。ZNF545低表达患者腋窝淋巴结转移高于ZNF545高表达患者(χ²=4.709，P=0.030)，ZNF545表达水平与β-catenin、C-myc表达水平均呈负相关(r值分别为-0.553和-0.551，均P＜0.001)。ZNF545 低表达患者的5年总生存(OS)率(58.0%)低于ZNF545高表达患者(84.2%)，差异有统计学意义(χ²=9.839,P=0.002)。多因素分析显示，ZNF545低表达(OR=2.462，95%CI 1.186~5.750，P=0.017)、组织学分级低(OR=2.650，95%CI 1.101~4.924，P=0.027)及有淋巴结转移(OR=6.307，95%CI 2.651~16.351，P＜0.001)是三阴性乳腺癌患者预后的独立危险因素。ZNF545低表达是三阴性乳腺癌患者腋窝淋巴结转移的独立危险因素(OR=2.355，95%CI 1.080~5.134，P=0.031)，且ZNF545表达水平与腋窝淋巴结转移数目呈负相关(r=-0.324 1,P=0.013)。结论:ZNF545低表达是三阴性乳腺癌患者预后和腋窝淋巴结转移的独立危险因素，其可能通过影响Wnt/β-catenin信号通路相关蛋白参与三阴性乳腺癌的进展。

Objective: To investigate the relationship between zinc finger protein 545(ZNF545) expression and prognosis and axillary lymph node metastasis in triple negative breast cancer(TNBC). Methods: The expression levels of ZNF545 and Wnt/β-catenin signaling pathway related proteins(β-catenin and C-myc) in 107 cancer issues of TNBC patients were detected by immunohistochemical staining. Logistic multivariate analysis was used to analyze the influencing factors of axillary lymph node metastasis of TNBC. Kaplan-Meier method was used to analyze the single factor survival of patients with TNBC. Cox proportional hazard regression model was used to analyze the independent prognostic factors of TNBC patients. Results: There were 50 cases(46.7%) with low expression of ZNF545 in TNBC. The axillary lymph node metastasis rate of ZNF545 low expression group was higher than that of ZNF545 high expression group(χ²=4.709，P=0.030). The expression level of ZNF545 was negatively correlated with the expression levels of β-catenin and C-myc(r=-0.553 and -0.551, respectively,P<0.001).The 5-year overall survival(OS) rate of ZNF545 low expression group(58.0%) was lower than that of ZNF545 high expression group(84.2%), and the difference was statistically significant(χ²=9.839, P=0.002). Multivariate analysis showed that lower expression of ZNF545(OR=2.462,95%CI 1.186-5.750,P=0.017),lower histological grade(OR=2.650,95%CI 1.101-4.924,P=0.027) and lymph node metastasis(OR=6.307,95%CI 2.651-16.351,P＜0.001)were independent prognostic risk factors for patients with TNBC. Low expression of ZNF545 was an independent risk factor for axillary lymph node metastasis in patients with TNBC(OR=2.355，95%CI 1.080-5.134，P=0.031). The expression level of ZNF545 was negatively correlated with the number of axillary lymph node metastases(r=-0.324 1，P=0.013). Conclusion: Low expression of ZNF545,which may be involved in the process of TNBC by affecting Wnt/β-catenin signaling pathway related proteins, is an independent risk factor of prognosis and axillary lymph node metastasis in patients with TNBC.

参考文献：

[1] BARANOVA A,KRASNOSELSKYI M,STARIKOV V,et al.Triple-negative breast cancer: current treatment strategies and factors of negative prognosis[J].J Med Life,2022,15(2):153-161.
[2] HEY J,HALPERIN C,HARTMANN M,et al.DNA methylation landscape of tumor-associated macrophages reveals pathways,transcription factors,and prognostic value relevant to triple-negative breast cancer patients[J].Int J Cancer,2023,152(6):1226-1242.
[3] YANG P,WANG Y,MACFARLAN T S.The role of KRAB-ZFPs in transposable element repression and mammalian evolution[J].Trends Genet,2017,33(11):871-881.
[4] LUPO A,CESARO E,MONTANO G,et al.KRAB-zinc finger proteins: a repressor family displaying multiple biological functions[J].Curr Genomics,2013,14(4):268-278.
[5] 孙雨露,尤鑫,赵怡欣,等.肿瘤浸润淋巴细胞在三阴性乳腺癌中作用的研究进展[J].东南大学学报(医学版),2021,40(2):243-247.
[6] 唐燕,张喆.PDL1和Ki67在三阴性乳腺癌中的表达及其与临床病理资料的相关性分析[J].现代医学,2021,49(7):793-797.
[7] WANG S,WONG C C,ZHANG Y,et al.ZNF545 loss promotes ribosome biogenesis and protein translation to initiate colorectal tumorigenesis in mice[J].Oncogene,2021,40(48):6590-6600.
[8] DONG B,YANG Y,HAN A,et al.Ectopic expression of HSDL2 is related to cell proliferation and prognosis in breast cancer[J].Cancer Manag Res,2019,12(11):6531-6542.
[9] CHENG Y,LIANG P,GENG H,et al.A novel 19q13 nucleolar zinc finger protein suppresses tumor cell growth through inhibiting ribosome biogenesis and inducing apoptosis but is frequently silenced in multiple carcinomas[J].Mol Cancer Res,2012,10(7):925-936.
[10] 潘烽平,陈一鹏,李彦,等.锌指蛋白545对结直肠癌上皮间质转化和迁移侵袭的影响[J].浙江医学,2020,42(7):656-659.
[11] DENG S,XIANG J J,GE H P,et al.The role of MIR-186 and ZNF545 in inhibiting the proliferation of multiple myeloma cells[J].J Biol Regul Homeost Agents,2019,33(3):721-729.
[12] DENG J,LIANG H,YING G,et al.Poor survival is associated with the methylated degree of zinc-finger protein 545(ZNF545) DNA promoter in gastric cancer[J].Oncotarget,2015,6(6):4482-4495.
[13] YANG W,YANG S,ZHANG M,et al.ZNF545 suppresses human hepatocellular carcinoma growth by inhibiting NF-κB signaling[J].Genes Cancer,2017,8(3-4):528-535.

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