Tip60蛋白在子宫内膜腺癌组织中的表达及其临床意义

doi:10.13481/j.1671-587X.20210523

Abstract

Abstract: Objective

To investigate the relationships between the expression of Tip60 protein in the endometrial adenocarcinoma tissue and the clinicopathological parameters and prognosis of endometrial adenocarcinoma，and to clarify the effect of Tip60 protein in the occurrence and development of endometrial adenocarcinoma.

Methods

A toatal of 84 cases of endometrial adenocarcinoma patients were selected. The expression levels of Tip60 protein in 84 cases of endometrial adenocarcinoma tissue and 36 cases of normal endometrial tissue were selected with immunohistochemical SP method. The relationships between the expression of Tip60 protein and the clinicopathological parameters were analyzed. Kaplan-Meier curve was used to analyze the relationships between the expression of Tip60 protein and prognosis of the patients. Western blotting method was used to detect the expressions of Tip60 in the endometrial carcinoma cell lines ISHIKAWA and HEC-1A.

Results

The immunohistochemistry results showed that the positive expression rate of Tip60 protein in the endometrial adenocarcinoma tissue was 54.76% （46/84）， which was significantly lower than that in the normal endometrial tissue （83.33%， 30/36）（χ²=8.859，P=0.003）.The expression of Tip60 protein was not associated with age of the patients（χ²=1.073，P=0.300）； the positive expression rate of Tip60 protein in endometrial adenocarcinoma tissue of the patients in grade Ⅰ of FIGO stage was significantly high than those of the patients in grade Ⅰ and grade Ⅲ（χ²=13.481，P=0.001）；the positive expression rate of Tip60 protein in the endometrial adenocarcinoma patients with high differentiation was higher than that in the patients with low and middle differentiation（χ²=8.962，P=0.013）. The median follow-up time for 84 patients with endometrial adenocarcinoma was 58 months. The results of Kaplan-Meier survival analysis and Log-rank test showed that the survival rate of the patients with high expression of Tip60 protein was significantly higher than that of the patients with low expression（χ²=64.391， P=0.002）. The expression level of Tip60 protein in the ISHIKAWA cells with high expression of estrogen receptor（ER） was significantly higher than that of HEC-1A cells with low expression of ER （P<0.05）.

Conclusion

The expressions of Tip60 protein in endometrial adeno carcinoma tissue and Ishikawa cells with high expression of ER are lower which suggests that Tip60 protein is involved in the occurrence and development of endometrial adenocarcinoma. The detection of Tip60 protein expression level in endometrial tissue is helpful for the diagnosis and prognosis of endometrial adenocarcinoma.

Key words: Tip60 protein, endometrial carcinoma, pathological characteristic, prognosis, immunohistochemistry

CLC Number:

R737.33

Aiping WEN,Le LUO,Zhiwei MENG,Jingji JIN,Honggui ZHOU,Jihong ZHU. Expression of Tip60 protein in endometrial adenocarcinoma tissue and its clinical significance[J].Journal of Jilin University(Medicine Edition), 2021, 47(5): 1244-1249.

Figures/Tables 4

Fig.1

Tab.1

Fig.2

Fig.3

References 19

1	周琦，吴小华，刘继红，等. 子宫内膜癌诊断与治疗指南（第四版）［J］. 中国实用妇科与产科杂志， 2018， 34（8）： 880-886.
2	杨丹，韩立敏. 1969－2003年子宫内膜癌发病率及发病因素分析［J］. 复旦学报（医学版）， 2005， 32（4）： 479-480， 483.
3	KOH W J， ABU-RUSTUM N R， BEAN S， et al. Uterine neoplasms， version 1.2018， NCCN clinical practice guidelines in oncology［J］. J Natl Compr Canc Netw， 2018， 16（2）： 170-199.
4	KAMINE J， ELANGOVAN B， SUBRAMANIAN T， et al. Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator［J］. Virology， 1996， 216（2）： 357-366.
5	SUN Y， JIANG X， CHEN S， et al. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM［J］. PNAS， 2005， 102（37）： 13182-13187.
6	COFFEY K， BLACKBURN T J， COOK S， et al. Characterisation of a Tip60 specific inhibitor， NU9056， in prostate cancer［J］. PLoS One， 2012， 7（10）： e45539.
7	BROECKAVAN DEN， NISSOU D， BRAMBILLA E， et al. Activation of a Tip60/E2F1/ERCC1 network in human lung adenocarcinoma cells exposed to cisplatin［J］. Carcinogenesis， 2012， 33（2）： 320-325.
8	PATEL J H， DU Y， ARD P G， et al. The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60［J］. Mol Cell Biol， 2004， 24（24）： 10826-10834.
9	MURR R， LOIZOU J I， YANG Y G， et al. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks［J］. Nat Cell Biol， 2006， 8（1）： 91-99.
10	CHAILLEUX C， TYTECA S， PAPIN C， et al. Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex［J］. Biochem J， 2010， 426（3）： 365-371.
11	CHEN G D， CHENG Y B， TANG Y， et al. Role of Tip60 in human melanoma cell migration， metastasis， and patient survival［J］. J Investig Dermatol， 2012， 132（11）： 2632-2641.
12	LAURBERG J R， BREMS-ESKILDSEN A S， NORDENTOFT I， et al. Expression of TIP60 （tat-interactive protein） and MRE11 （meiotic recombination 11 homolog） predict treatment-specific outcome of localised invasive bladder cancer［J］. BJU Int， 2012， 110（11 c）： E1228-E1236.
13	孙伟. 凋亡相关基因及其交互作用与食管鳞癌生物学特性的临床研究［D］. 乌鲁木齐：新疆医科大学， 2010.
14	MCGUIRE A， CASEY M C， SHALABY A， et al. Quantifying Tip60 （Kat5） stratifies breast cancer［J］. Sci Rep， 2019， 9（1）： 3819.
15	ZHANG Y， JI G， HAN S， et al. Tip60 suppresses cholangiocarcinoma proliferation and metastasis via PI3k-AKT［J］. Cell Physiol Biochem， 2018， 50（2）： 612-628.
16	TAN K N， AVERY V M， CARRASCO-POZO C. Metabolic roles of androgen receptor and Tip60 in androgen-dependent prostate cancer［J］. Int J Mol Sci， 2020， 21（18）： 6622.
17	IDRISSOU M， LEBERT A， BOISNIER T， et al. Digging deeper into breast cancer epigenetics： insights from chemical inhibition of histone acetyltransferase TIP60 in vitro ［J］. Omics， 2020， 24（10）： 581-591.
18	罗乐，杨陈武，敬巧，等. Tip60蛋白在上皮性卵巢癌组织中的表达及其与患者预后的关系［J］. 癌症进展， 2020， 18（14）： 1449-1452.
19	文爱平，汪海娇，罗乐，等. hMOF蛋白在子宫内膜癌组织中的表达及临床意义［J］. 中国实验诊断学， 2011， 15（10）： 1648-1651.

Clinicopathological feature	Tip60 protein [n(η/%)]			χ²	P
Clinicopathological feature	Positive	Negative		χ²	P
Age（year）
≥50	27（60.00）	18(40.00)	1.073		0.300
<50	19（48.71）	20(51.29)	1.073		0.300
Histologicalgrade
High	25（71.43）	10(28.57)
Middle	14（51.85）	13(48.15)	8.692		0.013
Low	7（31.82）	15(62.18)
FIGO stage
Ⅰ	30（76.92）	9(23.08)
Ⅱ	11(55.00)	9(45.00)	17.323		0.001
Ⅲ-Ⅳ	6(24.00)	19(76.00)

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Expression of Tip60 protein in endometrial adenocarcinoma tissue and its clinical significance

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