Expression of XPO4, MAP2K4 and ZIC1 in endometrial cancer tissues and prognostic value in endometrial cancer patient

doi:10.3877/cma.j.issn.1673-5250.2021.04.005

Objective

To explore expression of exportin (XPO)4, mitogen-activated protein kinase (MAP2K)4 and zinc finger protein of cerebellum (ZIC)1 in endometrial cancer (EC) tissues and their prognostic values in EC patient.

Methods

From June 2017 to June 2018, a total of 147 EC patients admitted to Wuxi Maternal and Child Health Hospital and Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University were selected as research subjects. Expression levels of XPO4, MAP2K4 and ZIC1 in EC tissues and adjacent normal tissues of EC patients were detected by immunohistochemical staining method. Positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues and adjacent normal tissues of EC patients, as well as positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues of EC patients with different clinicopathological characteristics were compared by chi-square test. Two-stage test was used to compare 3-year overall survival (OS) rates of EC patients with XPO4, MAP2K4, ZIC1 positive expression and negative expression in EC tissues. This study was approved by the Ethics Committee of Wuxi Maternal and Child Health Hospital and Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University (approval No. 20160803, 20160502).

Results

①The positive rates of XPO4 and MAP2K4 in EC tissues of EC patients were 34.7% (51/147) and 38.1% (56/147) respectively, which were statistically lower than those in adjacent normal tissues 66.7% (98/147) and 72.8% (107/147), and both differences were statistically significant (χ²=30.060, 35.812; P<0.001). The positive rate of ZIC1 in EC tissues of EC patients was 72.1% (106/147), which was statistically higher than that in adjacent normal tissues 40.1% (59/147), and the difference was statistically significant (χ²=30.512, P<0.001). ②The positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues of EC patients with different age, EC diameter and menopausal or not were compared, and the differences were not statistically significant (P>0.05). While there were statistically significant differences in the positive rates of XPO4, MAP2K4 and ZIC1 in EC tissues of EC patients with different International Federation of Obstetrics and Gynecology (FIGO) stages, histopathological grades, myometrial invasion degree, and lymph node metastasis (P<0.05). ③The 3-year OS rates of EC patients with negative expression of XPO4 and MAP2K4 were 42.7% and 38.5% respectively, which were statistically lower than those of patients with positive expression of XPO4 and MAP2K4 68.6% and 71.4%, and both differences were statistically significant (χ²=8.960, P=0.003; χ²=15.077, P<0.001). The 3-year OS rate of EC patients with positive expression of ZIC1 was 35.8%, which was statistically lower than that of patients with ZIC1 negative expression, and the difference was statistically significant (χ²=12.579, P<0.001).

Conclusions

XPO4 and MAP2K4 are lowly expressed, and ZIC1 is highly expressed in EC tissues. Expression levels of XPO4, MAP2K4 and ZIC1 are related to the histopathological grade, lymph node metastasis, FIGO stage, myometrial invasion, and 3-year OS rate of EC patients, and they have certain values in assessing the development, progression and prognosis of EC patients.

Key words: Endometrial neoplasms, Exportin-4, Mitogen-activated protein kinase 4, Zinc finger protein of cerebellum 1, Prognosis, Female

表1 本组EC患者EC组织及癌旁正常组织的XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]

组别	例数	XPO4	MAP2K4	ZIC1
EC组织	147	51(34.7)	56(38.1)	106(72.1)
癌旁正常组织	147	98(66.7)	107(72.8)	59(40.1)
χ²值		30.060	35.812	30.512
P值		<0.001	<0.001	<0.001

表1 本组EC患者EC组织及癌旁正常组织的XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]

组别	例数	XPO4	MAP2K4	ZIC1
EC组织	147	51(34.7)	56(38.1)	106(72.1)
癌旁正常组织	147	98(66.7)	107(72.8)	59(40.1)
χ²值		30.060	35.812	30.512
P值		<0.001	<0.001	<0.001

图1 本组1例EC患者(38岁，FIGO分期为Ⅱ期，伴淋巴结转移)EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1免疫组化检测结果(图1A：EC组织XPO4检测结果；图1B：癌旁正常组织XPO4检测结果；图1C：EC组织MAP2K4检测结果；图1D：癌旁正常组织MAP2K4检测结果；图1E：EC组织ZIC1检测结果；图1F：癌旁正常组织ZIC1检测结果)(免疫组化染色，高倍)

表2 本组EC患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]

类别			例数	XPO4			MAP2K4			ZIC1
类别			例数	阳性	χ²值	P值	阳性	χ²值	P值	阳性	χ²值	P值
年龄(岁)					0.027	0.869		0.098	0.754		0.529	0.467
		<50	27	9(33.3)			11(40.7)			21(77.8)
		≥50	120	42(35.0)			45(37.5)			85(70.8)
EC直径(cm)					0.061	0.804		0.013	0.910		0.037	0.847
		<4.0	77	26(33.8)			29(37.7)			55(71.4)
		≥4.0	70	25(35.7)			27(38.6)			51(72.9)
绝经					0.005	0.942		0.034	0.853		0.028	0.866
	否		38	13(34.2)			14(36.8)			27(71.1)
	是		109	38(34.9)			42(38.5)			79(72.5)
FIGO分期(期)					6.565	0.010		6.491	0.011		9.525	0.002
	Ⅰ~Ⅱ		115	46(40.0)			50(43.5)			76(66.1)
	Ⅲ		32	5(15.6)			6(18.8)			30(93.8)
组织病理学分级(级)					3.963	0.047		5.236	0.022		6.032	0.014
	G1~G2		127	48(37.8)			53(41.7)			87(68.5)
	G3		20	3(15.0)			3(15.0)			19(95.0)
子宫肌层侵犯(%)					8.434	0.004		9.046	0.003		15.640	<0.001
	<50		105	44(41.9)			48(45.7)			66(62.9)
	≥50		42	7(16.7)			8(19.0)			40(95.2)
淋巴结转移					9.407	0.002		9.884	0.002		8.746	0.003
	否		107	45(42.1)			49(45.8)			70(65.4)
	是		40	6(15.0)			7(17.5)			36(90.0)

表2 本组EC患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]

类别			例数	XPO4			MAP2K4			ZIC1
类别			例数	阳性	χ²值	P值	阳性	χ²值	P值	阳性	χ²值	P值
年龄(岁)					0.027	0.869		0.098	0.754		0.529	0.467
		<50	27	9(33.3)			11(40.7)			21(77.8)
		≥50	120	42(35.0)			45(37.5)			85(70.8)
EC直径(cm)					0.061	0.804		0.013	0.910		0.037	0.847
		<4.0	77	26(33.8)			29(37.7)			55(71.4)
		≥4.0	70	25(35.7)			27(38.6)			51(72.9)
绝经					0.005	0.942		0.034	0.853		0.028	0.866
	否		38	13(34.2)			14(36.8)			27(71.1)
	是		109	38(34.9)			42(38.5)			79(72.5)
FIGO分期(期)					6.565	0.010		6.491	0.011		9.525	0.002
	Ⅰ~Ⅱ		115	46(40.0)			50(43.5)			76(66.1)
	Ⅲ		32	5(15.6)			6(18.8)			30(93.8)
组织病理学分级(级)					3.963	0.047		5.236	0.022		6.032	0.014
	G1~G2		127	48(37.8)			53(41.7)			87(68.5)
	G3		20	3(15.0)			3(15.0)			19(95.0)
子宫肌层侵犯(%)					8.434	0.004		9.046	0.003		15.640	<0.001
	<50		105	44(41.9)			48(45.7)			66(62.9)
	≥50		42	7(16.7)			8(19.0)			40(95.2)
淋巴结转移					9.407	0.002		9.884	0.002		8.746	0.003
	否		107	45(42.1)			49(45.8)			70(65.4)
	是		40	6(15.0)			7(17.5)			36(90.0)

图2 本组EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性EC患者的OS曲线分析(图2A：XPO4呈阳性与呈阴性EC患者OS曲线；图2B：MAP2K4呈阳性与呈阴性EC患者OS曲线；图2C：ZIC1呈阳性与呈阴性EC患者OS曲线)

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