Prospero相关同源异形盒蛋白1在乳腺癌组织中的表达及与预后相关性分析
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摘要
背景与目的:Prospero相关同源异形盒蛋白1(prospero-related homeobox 1,PROX1)作为同源域转录因子家族成员,参与多种恶性肿瘤的发生、发展过程,与肿瘤细胞增殖、分化、凋亡、迁移和侵袭过程密切相关。该研究探讨了PROX1在乳腺癌组织中的表达及与预后相关性分析。方法:选取2011年3月—2013年3月在郑州市第三人民医院择期行手术治疗且资料完整的乳腺癌患者85例,采用免疫组织化学染色法检测乳腺癌和癌旁组织中PROX1蛋白水平,所有患者术后随访。随访中,失访4例,随访截止日期为2018年3月31日,生存分析采用Kaplan-Meier法和Log-rank检验,乳腺癌患者预后影响因素分析采用Cox比例风险回归模型。结果:乳腺癌组织中PROX1蛋白阳性率为71.76%,癌旁组织则为28.57%,差异有统计学意义(χ~2=32.600,P<0.001);乳腺癌组织中PROX1蛋白水平在不同分化程度、TNM分期、雌激素受体(estrogen receptor,ER)、Ki-67标记指数和淋巴结转移患者之间的差异有统计学意义(P<0.05);Kaplan-Meier生存分析结果显示,PROX1阳性表达组平均生存时间为(36.73±2.73)个月,PROX1阴性表达组则为(56.36±2.13)个月,Log-rank检验结果差异有统计学意义(χ~2=11.803,P=0.001);Cox比例风险回归模型结果显示,分化程度、TNM分期、淋巴结转移和PROX1蛋白表达是影响乳腺癌患者预后的风险因素(P<0.05)。结论:PROX1蛋白在乳腺癌组织中呈高表达,且与乳腺癌发生、进展及预后密切相关,是影响患者预后的风险因素。
Background and purpose: Prospero-related homeobox 1(PROX1), a member of the homeodomain transcription factor family, is involved in the development and progression of a variety of malignant tumors, and is closely related to tumor cell proliferation, differentiation, apoptosis, migration and invasion. This study explored the expression of PROX1 in breast cancer tissues and its correlation with prognosis. Methods: A total of 85 patients with breast cancer underwent elective surgery, and complete data were collected from Mar. 2011 to Mar. 2013. Immunohistochemical staining was used to detect the protein level of PROX1 in breast cancer and adjacent tissues. All patients were followed up, and 4 patients were lost during follow-up. Follow-up deadline was Mar. 31, 2018. Kaplan-Meier method and Log-rank test were used for survival analysis. Cox proportional hazards regression model was used to analyze the prognostic factors of breast cancer. Results: The positive rate of PROX1 protein was 71.76% in breast cancer tissues and 28.57% in adjacent tissues(χ~2=32.600, P<0.001). The expression of PROX1 protein in breast cancer tissues was significantly different in the degree of differentiation, TNM stage, estrogen receptor(ER), Ki-67 labeling index and lymph node metastasis compared with adjacent tissues(P<0.05). Kaplan-Meier survival analysis showed that the mean survival time of the PROX1 positive expression group was(36.73±2.73) months, and that of the PROX1 negative expression group was(56.36±2.13) months. The Log-rank test showed the difference in mean survival time was statistically significant between the two groups(χ~2=11.803, P=0.001). The Cox proportional hazards regression model showed that the degree of differentiation, TNM stage, lymph node metastasis and PROX1 protein expression were risk factors for the prognosis of breast cancer patients(P<0.05). Conclusion: PROX1 is highly expressed in breast cancer tissues, and is closely related to the occurrence and progression of breast cancer and prognosis of patients. It is a risk factor affecting the prognosis of patients.
Background and purpose: Prospero-related homeobox 1(PROX1), a member of the homeodomain transcription factor family, is involved in the development and progression of a variety of malignant tumors, and is closely related to tumor cell proliferation, differentiation, apoptosis, migration and invasion. This study explored the expression of PROX1 in breast cancer tissues and its correlation with prognosis. Methods: A total of 85 patients with breast cancer underwent elective surgery, and complete data were collected from Mar. 2011 to Mar. 2013. Immunohistochemical staining was used to detect the protein level of PROX1 in breast cancer and adjacent tissues. All patients were followed up, and 4 patients were lost during follow-up. Follow-up deadline was Mar. 31, 2018. Kaplan-Meier method and Log-rank test were used for survival analysis. Cox proportional hazards regression model was used to analyze the prognostic factors of breast cancer. Results: The positive rate of PROX1 protein was 71.76% in breast cancer tissues and 28.57% in adjacent tissues(χ~2=32.600, P<0.001). The expression of PROX1 protein in breast cancer tissues was significantly different in the degree of differentiation, TNM stage, estrogen receptor(ER), Ki-67 labeling index and lymph node metastasis compared with adjacent tissues(P<0.05). Kaplan-Meier survival analysis showed that the mean survival time of the PROX1 positive expression group was(36.73±2.73) months, and that of the PROX1 negative expression group was(56.36±2.13) months. The Log-rank test showed the difference in mean survival time was statistically significant between the two groups(χ~2=11.803, P=0.001). The Cox proportional hazards regression model showed that the degree of differentiation, TNM stage, lymph node metastasis and PROX1 protein expression were risk factors for the prognosis of breast cancer patients(P<0.05). Conclusion: PROX1 is highly expressed in breast cancer tissues, and is closely related to the occurrence and progression of breast cancer and prognosis of patients. It is a risk factor affecting the prognosis of patients.
引文
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[13]LEE Y G,KOH G Y.Coordinated lymphangiogenesis is critical in lymph node development and maturation[J].Dev Dyn,2016,245(12):1189-1197.
[14]XU X,WAN X,WEI X.PROX1 promotes human glioblastoma cell proliferation and invasion via activation of the nuclear factor-κB signaling pathway[J].Mol Med Rep,2017,15(2):963-968.
[15]DROSOS Y,NEALE G,YE J,et al.Prox1-heterozygosis sensitizes the pancreas to oncogenic K-ras-induced neoplastic transformation[J].Neoplasia,2016,18(3):172-184.
[16]VERSMOLD B,FELSBERG J,MIKESKA T,et al.Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer[J].Int J Cancer,2007,121(3):547-554.
[17]张逸群,叶双梅,蒋学锋,等.Prox1在乳腺癌组织中的表达及其与淋巴道转移的关系[J].肿瘤防治研究,2010,37(7):777-780.
[18]GAO T,MA C,LI Y,et al.High expression of prospero-related homeobox-1(PROX1)is associated with poor prognosis in patients with salivary adenoid cystic carcinoma[J].J Oral Maxillofac Surg,2018,76(7):1440-1446.
[2]HUANG T T,PENNARUN N,CHENG Y H,et al.Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients[J].Oncotarget,2018,9(33):23173-23182.
[3]SHIAO J,THOMAS K M,RAHIMI A S,et al.Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in stageⅡandⅢtriplenegative breast cancer patients[J].Breast Cancer Res Treat,2017,161(3):463-471.
[4]PAN Y,XIA L.Emerging roles of podoplanin in vascular development and homeostasis[J].Front Med,2015,9(4):421-430.
[5]ZHANG S,YU N,WANG L,et al.Prox1 represses IL-2 gene expression by interacting with NFAT2[J].Oncotarget,2017,8(41):69422-69434.
[6]RUDZINSKA M,LEDWON J K,GAWEL D,et al.The role of prospero homeobox 1(PROX1)expression in follicular thyroid carcinoma cells[J].Oncotarget,2017,8(69):114136-114155.
[7]黄三钱,钟晶敏,李晶,等.乳腺癌分子分型的研究进展[J].现代生物医学进展,2016,16(22):4384-4387,4269.
[8]张明明,贾晓梅,高伟.Vav1蛋白在胃癌中的表达及其临床意义[J].中国现代医学杂志,2018,28(8):35-38.
[9]KIM G R,CHOI J S,HAN B K,et al.Preoperative axillary US in early-stage breast cancer:potential to prevent unnecessary axillary lymph node dissection[J].Radiology,2018,288(1):55-63.
[10]税璘,沈丹,陈晓品.早期乳腺癌前哨淋巴结阳性患者腋窝管理方式的研究进展[J].临床肿瘤学杂志,2017,22(7):654-657.
[11]JATOI I,BENSON J R.Surgical management of the axilla in early breast cancer[J].Curr Probl Surg,2018,55(2):47-65.
[12]RAGUSA S,CHENG J,IVANOV K I,et al.PROX1 promotes metabolic adaptation and fuels out growth of Wnt(high)metastatic colon cancer cells[J].Cell Rep,2014,8(6):1957-1973.
[13]LEE Y G,KOH G Y.Coordinated lymphangiogenesis is critical in lymph node development and maturation[J].Dev Dyn,2016,245(12):1189-1197.
[14]XU X,WAN X,WEI X.PROX1 promotes human glioblastoma cell proliferation and invasion via activation of the nuclear factor-κB signaling pathway[J].Mol Med Rep,2017,15(2):963-968.
[15]DROSOS Y,NEALE G,YE J,et al.Prox1-heterozygosis sensitizes the pancreas to oncogenic K-ras-induced neoplastic transformation[J].Neoplasia,2016,18(3):172-184.
[16]VERSMOLD B,FELSBERG J,MIKESKA T,et al.Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer[J].Int J Cancer,2007,121(3):547-554.
[17]张逸群,叶双梅,蒋学锋,等.Prox1在乳腺癌组织中的表达及其与淋巴道转移的关系[J].肿瘤防治研究,2010,37(7):777-780.
[18]GAO T,MA C,LI Y,et al.High expression of prospero-related homeobox-1(PROX1)is associated with poor prognosis in patients with salivary adenoid cystic carcinoma[J].J Oral Maxillofac Surg,2018,76(7):1440-1446.