LSD1和PDPN在舌鳞状细胞癌中的表达及对预后的影响

摘要/Abstract

摘要：

目的探讨组蛋白赖氨酸特异性去甲基化酶1(LSD1)、平足蛋白(PDPN)在舌鳞状细胞癌组织中的表达及其与患者临床病理特征和预后的关系。方法选取新疆医科大学第一附属医院2011年1月至2016年1月67例舌鳞状细胞癌及相应癌旁正常组织标本,采用免疫组织化学法检测癌组织及癌旁组织中LSD1、PDPN的表达情况,并长期随访患者,分析LSD1和PDPN的表达与患者临床病理特征和预后的相互关系。结果LSD1和PDPN在舌鳞状细胞癌组织中的表达强度高于癌旁组织,差异具有统计学意义(Z=6.089,P<0.001;Z=5.781,P<0.001)。LSD1和PDPN的表达强度在不同临床分期(χ²=11.487,P=0.001;χ²=8.111,P=0.004)、淋巴结转移(χ²=4.772,P=0.029;χ²=6.206,P=0.013)、肿瘤大小(χ²=5.985,P=0.014;χ²=4.247,P=0.039)患者中差异均具有统计学意义。LSD1的表达强度在不同分化程度患者中差异也具有统计学意义(χ²=6.660,P=0.010)。单因素分析中,LSD1表达强度与患者无进展生存期(PFS)及总生存期(OS)呈负相关(χ²=18.930,P<0.001;χ²=16.257,P<0.001),PDPN表达强度与患者PFS及OS呈负相关(χ²=31.720,P<0.001;χ²=18.390,P<0.001),肿瘤大小与患者PFS和OS呈负相关(χ²=5.326,P=0.021;χ²=8.843,P=0.003);术后放疗、临床分期分别与患者的OS呈正、负相关(χ²=4.197,P=0.040;χ²=6.355,P=0.012)。多因素分析中,LSD1是患者PFS和OS的的独立危险因素(HR=5.743,95%CI为1.012~32.579,P=0.048;HR=17.759,95%CI为2.303~136.916,P=0.006),PDPN是患者PFS的独立危险因素(HR=4.380,95%CI为1.258~15.254,P=0.020),术后放疗是患者PFS及OS的保护因素(HR=0.374,95%CI为0.157~0.895,P=0.027;HR=0.218,95%CI为0.091~0.521,P=0.001),临床分期是患者OS的独立危险因素(HR=2.637,95%CI为1.107~6.280,P=0.029)。在舌鳞状细胞癌组织中,LSD1与PDPN的表达呈正相关(rs=0.655,P<0.001)。结论LSD1和PDPN在舌鳞状细胞癌组织中的表达均高于癌旁组织;LSD1是患者PFS和OS的独立危险因素,PDPN是患者PFS的独立危险因素,临床分期是患者OS的独立危险因素,术后放疗是患者PFS和OS的保护性因素。LSD1和PDPN在舌鳞状细胞癌中的表达呈正相关,二者可作为舌鳞状细胞癌患者预后的独立预测指标。

关键词:舌肿瘤,预后,组蛋白赖氨酸特异性去甲基化酶1,平足蛋白

Abstract:

ObjectiveTo investigate the expressions of lysine specific demethylase 1 (LSD1) and podoplanin (PDPN) in tongue squamous cell carcinoma and the correlation between LSD1 or PDPN and clinicopathological characteristics or prognosis.MethodsA total of 67 cases of tongue squamous cell carcinoma and corresponding paracancerous normal tissues in the First Affiliated Hospital of Xinjiang Medical University from January 2011 to January 2016 were selected. The expressions of LSD1 and PDPN in cancer and paracancerous tissues were detected by immunohistochemical method, and the patients were followed up for a long time to analyze the correlation between the expression of LSD1 or PDPN and clinicopathological characteristics or prognosis.ResultsThe expressions of LSD1 and PDPN in tongue squamous cell carcinoma tissues were higher than those in paracancerous tissues, and the differences were statistically significant (Z=6.089,P<0.001;Z=5.781,P<0.001). The expression intensities of LSD1 and PDPN were significantly different in patients with different clinical stage (χ²=11.487,P=0.001;χ²=8.111,P=0.004), lymph node metastasis (χ²=4.772,P=0.029;χ²=6.206,P=0.013) and tumor size (χ²=5.985,P=0.014;χ²=4.247,P=0.039). The expression intensity of LSD1 was also significantly different in patients with different degrees of differentiation (χ²=6.660,P=0.010). In univariate analysis, LSD1 expression intensity was negatively correlated with progression-free survival (PFS) and overall survival (OS) (χ²=18.930,P<0.001;χ²=16.257,P<0.001), PDPN expression intensity was negatively correlated with PFS and OS (χ²=31.720,P<0.001;χ²=18.390,P<0.001), and tumor size was negatively correlated with PFS and OS (χ²=5.326,P=0.021;χ²=8.843,P=0.003). Postoperative radiotherapy and clinical stage were positively and negatively correlated with OS respectively (χ²=4.197,P=0.040;χ²=6.355,P=0.012). In multivariate analysis, LSD1 was an independent risk factor for PFS and OS (HR=5.743, 95%CI: 1.012-32.579,P=0.048;HR=17.759, 95%CI: 2.303-136.916,P=0.006), PDPN was an independent risk factor for PFS (HR=4.380, 95%CI: 1.258-15.254,P=0.020), postoperative radiotherapy was a protective factor for PFS and OS (HR=0.374, 95%CI: 0.157-0.895,P=0.027;HR=0.218, 95%CI: 0.091-0.521,P=0.001), and clinical stage was an independent risk factor for OS (HR=2.637, 95%CI: 1.107-6.280,P=0.029). In tongue squamous cell carcinoma tissues, the expression of LSD1 was positively correlated with that of PDPN (rs=0.655,P<0.001).ConclusionThe expressions of LSD1 and PDPN in tongue squamous cell carcinoma are higher than those in adjacent tissues. LSD1 is an independent risk factor for PFS and OS, PDPN is an independent risk factor for PFS, clinical stage is an independent risk factor for OS, and postoperative radiotherapy is a protective factor for PFS and OS. There is a positive correlation between the expressions of LSD1 and PDPN in tongue squamous cell carcinoma, and they can both be used as independent predictors of prognosis in patients with tongue squamous cell carcinoma.

Key words:Tongue neoplasms,Prognosis,Lysine specific demethylase 1,Podoplanin

王坤龙, 张洋, 宿伟鹏, 刘攀, 赵化荣. LSD1和PDPN在舌鳞状细胞癌中的表达及对预后的影响[J]. 国际肿瘤学杂志, 2020, 47(5): 264-271.

Wang Kunlong, Zhang Yang, Su Weipeng, Liu Pan, Zhao Huarong. Expressions of LSD1 and PDPN in tongue squamous cell carcinoma and their effects on prognosis[J]. Journal of International Oncology, 2020, 47(5): 264-271.

图/表12

图1

组别	阴性	弱阳性	阳性	强阳性
癌组织	9	13	35	10
癌旁组织	53	7	3	4
Z值	6.089
P值	<0.001

表1

图2

组别	阴性	弱阳性	阳性	强阳性
癌组织	15	16	30	6
癌旁组织	56	3	7	1
Z值	5.781
P值	<0.001

表2

表3

LSD1和PDPN在舌鳞状细胞癌组织中的表达与患者临床病理特征的关系(例)"

临床病理特征	例数	LSD1					PDPN
临床病理特征	例数	低表达	高表达	χ²值	P值		低表达	高表达	χ²值	P值
性别
男	34	10	24	0.367	0.545	18		16	1.236	0.266
女	33	12	21			13		20
年龄(岁)
≤60	44	14	30	0.060	0.806	20		24	0.034	0.853
>60	23	8	15			11		12
肿瘤大小
T_1-2	48	20	28	5.985	0.014	26		22	4.247	0.039
T_3-4	19	2	17			5		14
分化程度
低、中	27	4	23	6.660	0.010	9		18	3.044	0.081
高	40	18	22			22		18
淋巴结转移
无	46	19	27	4.772	0.029	26		20	6.206	0.013
有	21	3	18			5		16
临床分期
Ⅰ~Ⅱ	35	18	17	11.487	0.001	22		13	8.111	0.004
Ⅲ~Ⅳ	32	4	28			9		23

表3

表4

67例舌鳞状细胞癌患者临床病理因素与患者PFS及OS的单因素分析(%)"

临床病理特征	无进展生存率						总生存率
临床病理特征	1年	3年	5年	χ²值	P值		1年	3年	5年	χ²值	P值
性别
男	67.6	58.8	52.6	0.116	0.734	82.4		67.6	58.1	0.015	0.902
女	69.7	51.5	48.5			81.8		63.6	59.1
年龄(岁)
≤60	68.2	56.8	52.2	0.042	0.837	84.1		68.2	59.6	0.139	0.710
>60	69.6	52.2	47.8			78.3		60.9	56.5
肿瘤大小
T_1-2	75.0	58.3	58.3	5.326	0.021	91.7		77.1	67.2	8.843	0.003
T_3-4	52.6	36.8	30.7			57.9		36.8	36.8
分化程度
低、中	55.6	51.9	51.9	0.154	0.694	70.4		55.6	51.3	1.580	0.209
高	77.5	57.5	49.6			90.0		72.5	63.9
淋巴结转移
无	76.1	58.7	54.3	1.437	0.231	93.5		71.7	60.9	1.530	0.216
有	52.4	47.6	42.9			57.1		52.4	52.4
临床分期
Ⅰ~Ⅱ	80.0	65.7	60.0	3.718	0.054	100.0		82.9	69.0	6.355	0.012
Ⅲ~Ⅳ	56.3	43.8	40.4			62.5		46.9	46.9
术后化疗
否	68.1	53.2	46.6	0.680	0.410	83.0		61.7	56.4	0.299	0.585
是	70.0	60.0	60.0			80.0		70.0	63.6
术后放疗
否	56.7	43.3	40.0	3.266	0.071	76.7		50.0	45.5	4.197	0.040
是	78.4	64.9	59.2			86.5		78.4	69.3
LSD1表达
低	95.5	90.9	90.9	18.930	<0.001	100.0		100.0	93.3	16.257	<0.001
高	55.6	35.6	30.8			73.3		48.9	41.5
PDPN表达
低	93.5	87.1	87.1	31.720	<0.001	100.0		90.3	87.1	18.390	<0.001
高	47.2	27.8	19.4			66.7		44.4	34.6

表4

表达强度	LSD1		PDPN
阴性	-			-	19.752	<0.001	-	31.769	<0.001	-	18.428	<0.001
弱阳性	-	20.260	<0.001	-			-			-
阳性	17			40			12			26
强阳性	9			12			6			9

表5

图3

图4

临床病理因素	B值	SE值	Wald值	P值	HR值	95%CI
术后放疗	-0.982	0.445	4.881	0.027	0.374	0.157~0.895
LSD1表达强度	1.748	0.886	4.051	0.048	5.743	1.012~32.579
PDPN表达强度	1.477	0.637	5.383	0.020	4.380	1.258~15.254

表6

临床病理因素	B值	SE值	Wald值	P值	HR值	95%CI
临床分期	0.970	0.443	4.795	0.029	2.637	1.107~6.280
术后放疗	-1.524	0.445	11.750	0.001	0.218	0.091~0.521
LSD1表达强度	2.877	1.042	7.621	0.006	17.759	2.303~136.916

表7

LSD1表达强度	PDPN表达强度	rs值	P值
阴性	9	0	0	0
弱阳性	2	9	1	1	0.655	<0.001
阳性	4	6	23	2
强阳性	0	1	6	3

表8

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