人FOXA1蛋白在卵巢上皮癌中的表达及其临床意义
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摘要
目的:探讨卵巢上皮癌患者病理组织中叉头盒蛋白A1(FOXA1)表达情况及其对卵巢癌预后的影响。方法:采集2015年1月至2017年11月于本院收治并经病理确诊的163例卵巢上皮癌患者肿瘤组织标本,应用免疫组织化学方法检测病理组织中人FOXA1蛋白表达的情况。应用Log-Rank检验比较低FOXA1蛋白表达患者与高FOXA1蛋白表达患者间的生存时间差异,并应用COX模型探索卵巢上皮癌预后的影响因素。结果:163例患者中FOXA1蛋白处于高表达水平的比例较高(74. 85%),并且FOXA1蛋白高度表达比例在不同肿瘤分期、不同肿瘤直径患者间的差异均有统计学意义(P <0. 05)。高表达FOXA1蛋白的患者生存时间较低表达FOXA1蛋白的患者生存时间短(P <0. 000 1);卵巢上皮癌患者病理组织中FOXA1蛋白高度表达是卵巢癌预后的风险因素(HR=2. 24)。结论:FOXA1蛋白表达在卵巢上皮癌的发生、发展中起着重要的作用,并且与患者预后有密切的关系。干预FOXA1的表达可成为延缓或控制卵巢上皮癌发展的可行方法。
Objective: To explore the express of Forkhead box A1( FOXA1) in human epithelial ovarian carcinoma( EOC) and the effects on EOC prognosis. Methods: Immunohistochemical analysis was performed to evaluate FOXA1 expression in 163 epithelial ovarian carcinoma tissue specimens. The present study analyzed the association between FOXA1 expression and clinical characteristics in the patients with EOC. Kaplan-Meier method was used for survival analysis. Results: The immunohistochemical expression of FOXA1 in EOC tissues was associated with the FIGO grade and diameter of tumor. The results of Kaplan-Meier survival curve revealed that high FOXA1 expression was associated with decreased overall survival time in the patients in relation with low FOXA1 expression( P < 0. 05). Conclusion: FOXA1 is over expressed in EOC and associated with clinicopathological features,including overall survival time. FOXA1 potentially represents a novel biomarker and therapeutic target for EOC.
Objective: To explore the express of Forkhead box A1( FOXA1) in human epithelial ovarian carcinoma( EOC) and the effects on EOC prognosis. Methods: Immunohistochemical analysis was performed to evaluate FOXA1 expression in 163 epithelial ovarian carcinoma tissue specimens. The present study analyzed the association between FOXA1 expression and clinical characteristics in the patients with EOC. Kaplan-Meier method was used for survival analysis. Results: The immunohistochemical expression of FOXA1 in EOC tissues was associated with the FIGO grade and diameter of tumor. The results of Kaplan-Meier survival curve revealed that high FOXA1 expression was associated with decreased overall survival time in the patients in relation with low FOXA1 expression( P < 0. 05). Conclusion: FOXA1 is over expressed in EOC and associated with clinicopathological features,including overall survival time. FOXA1 potentially represents a novel biomarker and therapeutic target for EOC.
引文
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[20]BADVE S,TURBIN D,THORAT M A,et al. FOXA1 expression in breast cancer--correlation with luminal subtype A and survival[J]. Clin Cancer Res,2007,13(15 Pt 1):4415-4421.
[2]刘梦娜,谢静燕,赵树立.雌激素受体在卵巢癌研究中的进展[J].东南大学学报(医学版),2014,33(2):215-218.
[3]李玉娟,赵树立,谢静燕.外泌体在卵巢癌中的研究进展[J].东南大学学报(医学版),2017,36(2):256-259.
[4]雷磊,王艳丽,梁静,等.卵巢上皮癌差异表达microRNAs的筛选研究[J].现代肿瘤医学,2013,21(2):398-402.
[5] SKIRNISDOTTIR I,SEIDAL T. Association of p21,p21 p27and p21 p53 status to histological subtypes and prognosis in low-stage epithelial ovarian cancer[J]. Cancer Genomics Proteomics,2013,10(1):27-34.
[6]LEE C K,SIMES R J,BROWN C,et al. A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer[J]. Ann Oncol,2013,24(4):937-943.
[7]付清茹,齐红岩,荣安娜.晚期卵巢上皮癌新辅助化疗的研究进展[J].医学综述,2017,23(5):891-895.
[8]YIN M,LI C,LI X,et al. Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer[J]. J Sur Oncol,2011,104(1):29-36.
[9]WILLIAMSON E A,WOLF I,O'KELLY J,et al. BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1)[J]. Oncogene,2006,25(9):1391-1399.
[10]HABASHY H O,POWE D G,RAKHA E A,et al. Forkheadbox A1(FOXA1)expression in breast cancer and its prognostic significance[J]. Eur J Cancer,2008,44(11):1541-1551.
[11] HAUPTMANN S,DU BOIS A,MEINHOLD-HERLEIN I,et al.[Histological grading of epithelial ovarian cancer. Review and recommendation][J]. Pathologe,2014,35(5):497-503.
[12]TORRE L A,TRABERT B,DESANTIS C E,et al. Ovarian cancer statistics,2018[J]. CA Cancer J Clin,2018,68(4):284-296.
[13]KAESTNER K H,KNOCHEL W,MARTINEZ D E. Unified nomenclature for the winged helix/forkhead transcription factors[J]. Genes Dev,2000,14(2):142-146.
[14]WANG K,GUAN C,FANG C,et al. Clinical significance and prognostic value of Forkhead box A1 expression in human epithelial ovarian cancer[J]. Oncol Lett,2018,15(4):4457-4462.
[15]KATOH M,IGARASHI M,FUKUDA H,et al. Cancer genetics and genomics of human FOX family genes[J]. Cancer Lett,2013,328(2):198-206.
[16]LIN L,MILLER C T,CONTRERAS J I,et al. The hepatocyte nuclear factor 3 alpha gene,HNF3alpha(FOXA1),on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas[J]. Cancer Res,2002,62(18):5273-5279.
[17]LI Z,TUTEJA G,SCHUG J,et al. Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer[J]. Cell,2012,148(1-2):72-83.
[18]SONG Y,WASHINGTON M K,CRAWFORD H C. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer[J]. Cancer Res,2010,70(5):2115-2125.
[19]BASSERES D S,D'ALO F,YEAP B Y,et al. Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing[J]. Lung Cancer,2012,77(1):31-37.
[20]BADVE S,TURBIN D,THORAT M A,et al. FOXA1 expression in breast cancer--correlation with luminal subtype A and survival[J]. Clin Cancer Res,2007,13(15 Pt 1):4415-4421.