
浏览全部资源
扫码关注微信
1.450052 郑州,郑州大学第一附属医院妇科
2.472000 河南 三门峡,黄河三门峡医院妇科
[任芳,E-mail:renfang@foxmail.com REN Fang, E-mail: renfang@foxmail.com
收稿:2020-06-07,
修回:2020-08-14,
纸质出版:2020-11-15
移动端阅览
任芳, 李彩瑜, 马源蔚, 等. 卵巢癌中组蛋白赖氨酸去甲基化酶的表达及其临床意义[J]. 第三军医大学学报, 2020,42(21):2116-2121.
Fang REN, Caiyu LI, Yuanwei MA, et al. Expression and clinical significance of histone lysine demethylase 5A in ovarian cancer[J]. Journal of Third Military Medical University, 2020, 42(21): 2116-2121.
任芳, 李彩瑜, 马源蔚, 等. 卵巢癌中组蛋白赖氨酸去甲基化酶的表达及其临床意义[J]. 第三军医大学学报, 2020,42(21):2116-2121. DOI: 10.16016/j.1000-5404.202006058.
Fang REN, Caiyu LI, Yuanwei MA, et al. Expression and clinical significance of histone lysine demethylase 5A in ovarian cancer[J]. Journal of Third Military Medical University, 2020, 42(21): 2116-2121. DOI: 10.16016/j.1000-5404.202006058.
目的
2
研究卵巢癌(ovarian cancer
OC)中组蛋白赖氨酸去甲基化酶(histone lysine demethylase
KDMs)的表达水平及其与生存预后和临床病理特征间的关系。
方法
2
分别应用配对
t
检验和Kaplan-Meier法研究公共数据库GEO和TCGA中KDM5A在不同卵巢组织中的表达差异及其与OC生存预后的关系;实时荧光定量PCR技术和组织芯片技术用于测定临床标本中KDM5A的表达情况,绘制临床标本中KDM5A mRNA表达热图和KDM5A蛋白分布图;Kaplan-Meier法绘制68例卵巢癌患者生存曲线;分析KDM5A与预后及病理参数间的关系使用卡方检验和Cox回归模型。
结果
2
对公共数据库资料和临床病例分析得到,无论在基因水平还是蛋白质水平,KDM5A在卵巢癌组织中的水平都高于正常卵巢组织,并且在卵巢癌患者中,KDM5A高表达者的生存预后都劣于低表达者,分析临床卵巢癌患者的病理信息发现,KDM5A高表达与更晚的FIGO分期(
P
=0.012)和淋巴结转移(
P
=0.005)具有相关性。
结论
2
KDM5A高表达促进卵巢癌的发生、侵袭和转移,并且可用于预测卵巢癌患者的生存预后。
Objective
2
To study the expression level of histone lysine demethylase 5A (KDM5A) in ovarian cancer (OC) and its association with prognosis and clinicopathological features.
Methods
2
Paired
t
-test and Kaplan-Meier analysis were employed to analyze the variation of KDM5A expression level in OC tissue and normal ovarian tissues and its level with survival rate in OC patients
based on the data from GEO and TCGA public databases. The expression of KDM5A in clinically collected OC tissues (51 samples by radical resection and 17 formalin-fixed samples) and normal ovarian tissues (40 samples by surgeries due to benign uterine diseases) was also examined by real-time quantitative PCR (RT-qPCR) and tissue microarray (TMA). The results were used to draw the expression heat map and protein distribution profile of KDM5A in normal and cancerous tissues. Kaplan-Meier analysis was used to plot the survival curve of the 68 OC patients.
Chi
-square test and Cox regression model were adopted to analyze the correlation between KDM5A level and prognosis as well as pathological parameters.
Results
2
According to the data from the public databases and clinical analyses
the expression of KDM5A at both mRNA and protein levels wa
s significantly higher in the OC tissues than normal ovarian tissues (
P
<
0.05)
and the OC patients with high KDM5A expression had poorer prognosis than those with low expression. Analysis of clinical pathological data showed that high expression level of KDM5A was associated with advanced stage by International Federation of Gynecology and Obstetrics (FIGO) staging (
P
=0.012) and lymph node metastasis (
P
=0.005).
Conclusion
2
The high expression of KDM5A contributes to the occurrence
invasion and metastasis of OC
and can be used to predict the prognosis of the patients.
COBURN S B, BRAY F, SHERMAN M E, et al . Inter-national patterns and trends in ovarian cancer incidence, overall and by histologic subtype[J ] . Int J Cancer, 2017, 140(11): 2451-2460. DOI:10.1002/ijc.30676.
CHEN W Q, ZHENG R S, BAADE P D, et al . Cancer statistics in China, 2015[J ] . CA Cancer J Clin, 2016, 66(2): 115-132. DOI:10.3322/caac.21338.
ALEKSANDRA KUJAWA K, LISOWSKA K M. Ovarian cancer—from biology to clinic[J]. Postepy Hig Med Dosw, 2015, 69: 1275-1290. DOI:10.5604/17322693.1184451.
HYUN K, JEON J, PARK K, et al . Writing, erasing and reading histone lysine methylations[J ] . Exp Mol Med, 2017, 49(4): 1-22. DOI:10.1038/emm.2017.11.
MCGRATH J C, TROJER P. Targeting histone lysine methylation in cancer[J]. Pharmacol Ther, 2015, 150: 1-22. DOI:10.1016/j.pharmthera.2015.01.002.
DEFEO-JONES D, HUANG P S, JONES R E, et al . Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product[J ] . Nature, 1991, 352(6332): 251-254. DOI:10.1038/352251a0.
CHRISTENSEN J, AGGER K, CLOOS P A C, et al . RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3[J ] . Cell, 2007, 128(6): 1063-1076. DOI:10.1016/j.cell.2007.02.003.
ZENG J, GE Z, WANG L, et al . The histone demethylase RBP2 is overexpressed in gastric cancer and its inhibition triggers senescence of cancer cells[J ] . Gastroenterology, 2010, 138(3): 981-992. DOI:10.1053/j.gastro.2009.10.004.
TENG Y C, LEE C F, LI Y S, et al . Histone demethylase RBP2 promotes lung tumorigenesis and cancer metastasis[J ] . Cancer Res, 2013, 73(15): 4711-4721. DOI:10.1158/0008-5472.CAN-12-3165.
ALLIS C D, JENUWEIN T. The molecular hallmarks of epigenetic control[J]. Nat Rev Genet, 2016, 17(8): 487-500. DOI:10.1038/nrg.2016.59.
BLAIR L P, CAO J, ZOU M R, et al . Epigenetic regulation by lysine demethylase 5 (KDM5) enzymes in cancer[J ] . Cancers, 2011, 3(1): 1383-1404. DOI:10.3390/cancers3011383.
TU S J, TENG Y C, YUAN C H, et al . The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif[J ] . Nat Struct Mol Biol, 2008, 15(4): 419-421. DOI:10.1038/nsmb.1400.
LONGBOTHAM J E, CHIO C M, DHARMARAJAN V, et al . Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling[J ] . Nat Commun, 2019, 10(1): 94. DOI:10.1038/s41467-018-07829-z.
GUTIERREZ G M, KONG E, HINDS P W. Master or slave: the complex relationship of RBP2 and pRb[J]. Cancer Cell, 2005, 7(6): 501-502. DOI:10.1016/j.ccr.2005.05.021.
LOPEZ-BIGAS N, KISIEL T A, DEWAAL DC, et al . Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differen-tiation[J ] . Mol Cell, 2008, 31(4): 520-530. DOI:10.1016/j.molcel.2008.08.004.
ZARGAR Z U, KIMIDI M R, TYAGI S. Dynamic site-specific recruitment of RBP2 by pocket protein p130 modulates H3K4 methylation on E2F-responsive promoters[J]. Nucleic Acids Res, 2018, 46(1): 174-188. DOI:10.1093/nar/gkx961.
LHEUREUX S, BRAUNSTEIN M, OZA A M. Epithelial ovarian cancer: Evolution of management in the era of precision medicine[J]. CA Cancer J Clin, 2019, 69(4): 280-304. DOI:10.3322/caac.21559.
LI L P, WANG L X, SONG P, et al . Critical role of histone demethylase RBP2 in human gastric cancer angiogenesis[J ] . Mol Cancer, 2014, 13(1): 1-13. DOI:10.1186/1476-4598-13-81.
WANG Z Y, YANG J, LIU C K, et al . High expression of retinoblastoma-binding protein 2 (RBP2) in patients with hepatocellular carcinoma and its prognostic significance[J ] . Med Sci Monit, 2017, 23: 2736-2744.
CUI J J, QUAN M, XIE D C, et al . A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism[J ] . Oncogene, 2020, 39(5): 1140-1151. DOI:10.1038/s41388-019-1051-8.
OSER M G, SABET A H, GAO W H, et al . The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis[J ] . Genes Dev, 2019, 33(23/24): 1718-1738. DOI:10.1101/gad.328336.119.
ZHOU D H, KANNAPPAN V, CHEN X, et al . RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma[J ] . Exp Mol Med, 2016, 48(6): e238. DOI:10.1038/emm.2016.37.
KUMAR A, KUMARI N, SHARMA U, et al . Reduction in H3K4me patterns due to aberrant expression of methyl-transferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications[J ] . Sci Rep, 2019, 9(1): 8189. DOI:10.1038/s41598-019-44733-y.
FENG T F, WANG Y, LANG Y, et al . KDM5A promotes proliferation and EMT in ovarian cancer and closely correlates with PTX resistance[J ] . Mol Med Rep, 2017, 16(3): 3573-3580. DOI:10.3892/mmr.2017.6960.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621