ALG2在口腔鳞状细胞癌中的表达及其预后诊断价值

doi:10.12439/kqhm.1005-4979.2024.05.005

摘要/Abstract

摘要：

目的：分析凋亡关联基因2（apoptosis-linked gene-2，ALG2）在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）组织中的表达及其与临床病理特征的相关性、预后诊断价值。方法： 实时定量聚合酶链反应（real-time quantitative polymerase chain reaction，RT-qPCR) 检测ALG2在5对新鲜OSCC组织、癌旁组织及OSCC细胞系、人口腔黏膜角质形成细胞（human oral keratinocytes，HOK）中的表达；免疫组织化学（immunohistochemistry，IHC）法检测ALG2在128对OSCC组织和癌旁组织中的表达，并分析其表达高低与临床病理特征及预后的相关性；利用TCGA数据库分析ALG2在OSCC组织中的表达及其预后诊断价值。结果： ALG2在OSCC组织和细胞系中的表达明显高于其在癌旁组织和HOK细胞中（P<0.05）；ALG2低表达组OSCC患者的总体生存率、无疾病生存率和无进展生存率均显著高于ALG2高表达组（P<0.05）；T分期、淋巴结转移、ALG2表达水平均是影响OSCC患者预后的因素（P<0.05），且ALG2表达是OSCC患者预后的一个独立预测因素（P<0.01）；ALG2对OSCC可能具有一定的诊断价值[曲线下面积（area under the curve，AUC）=0.807]。结论： ALG2在OSCC中高表达，且与患者预后不良有关，对OSCC可能具有一定的诊断价值。

关键词: 口腔鳞状细胞癌, 凋亡关联基因2, 预后

Abstract:

Objective: To analyze the expression of apoptosis-linked gene-2 (ALG2) in oral squamous cell carcinoma (OSCC) tissues and cell lines and its correlations with the clinicopathological features and prognosis of patients.Methods: The expression of ALG2 in 5 pairs of fresh OSCC tissues, paracancerous normal tissues, OSCC cell lines and human oral keratinocytes (HOK) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression levels of ALG2 in paraffin-embedded OSCC tissues and adjacent normal tissues specimens of 128 patients with OSCC were detected by immunohistochemistry (IHC). The correlation of ALG2 expression in OSCC tissues with the clinicopathological features and survival time of patients were analyzed. The expression of ALG2 in OSCC tissues and its diagnostic, prognostic value were detected in TCGA database. Results: The expression of ALG2 in OSCC tissues and cell lines was significantly higher than those in paracancerous tissues and HOK cells (P<0.05). The overall survival, disease free survival and progression-free survival of OSCC patients in the group with low ALG2 expression were significantly higher than those in the ALG2 high expression group (P<0.05). T stage, lymphatic metastasis, and ALG2 expression were all factors affecting the prognosis of OSCC patients (P<0.05). ALG2 expression was an independent predictor of the prognosis of OSCC patients (P<0.01). ALG2 may have some diagnostic value for OSCC [area under the curve (AUC)=0.807]. Conclusion: ALG2 is highly expressed in OSCC and it is associated with unfavorable prognosis of the patients, and it may have some diagnostic value for OSCC.

Key words: oral squamous cell carcinoma, apoptosis-linked gene-2, prognosis

中图分类号:

R739.8
R782

高瑞, 郭磊, 彭博, 贾骏. ALG2在口腔鳞状细胞癌中的表达及其预后诊断价值[J]. 《口腔颌面外科杂志》, 2024, 34(5): 357-364.

GAO Rui, GUO Lei, PENG Bo, JIA Jun. Expression of ALG2 in oral squamous cell carcinoma and its prognostic diagnostic value[J]. 《Journal of Oral and Maxillofacial Surgery》, 2024, 34(5): 357-364.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2024/V34/I5/357

图/表 9

表1 引物序列

Table 1 Primer sequences

基因名	上游引物(5'-3')	下游引物(5'-3')
ALG2	CGGCAAGTTGTCGGAGACG	CCTGGAGGTTGGGATGCTCT
β-actin	AGGGAAATCGT GCGTGAC	CGCTCATTGCCGATAGTG

图1 ALG2 mRNA在OSCC和其他肿瘤组织中的表达 A．ALG2 mRNA在OSCC组织（n=329）和正常组织（n=32）中的表达；B．ALG2 mRNA在32对配对的OSCC组织和癌旁组织中的表达；C．ALG2 mRNA在其他恶性肿瘤组织中的表达。*表示P<0.05，与正常组织比较；#表示P<0.05，与癌旁组织相比。

Figure 1 The expression of ALG2 mRNA in OSCC tissues and other tumor tissues

图2 ALG2 mRNA在OSCC组织和细胞系中的相对表达 A．ALG2 mRNA在OSCC细胞系（SCC-15、CAL-27、HSC-3、SCC-25）和HOK细胞中的相对表达水平；B．OSCC组织和配对癌旁组织中ALG2 mRNA的相对表达水平。*表示P<0.05，**表示P<0.01，***表示P<0.001，与HOK组比较；^#表示P<0.05，与癌旁组织比较。

Figure 2 The relative expression of ALG2 mRNA in OSCC tissues and cell lines

表2 免疫组织化学统计分析结果[n(%)]

Table 2 The results of immunohistochemical statistical analysis [n(%)]

组别	n	ALG2低表达	ALG2高表达	P值
OSCC组	128	21(16.4)	107(83.6)	0.013
癌旁组	128	98(76.6)	30(23.4)^①	0.071

图3 ALG2 蛋白在OSCC组织和癌旁组织中的表达 A、C．免疫组织化学法检测ALG2蛋白在癌旁组织中的表达；B、D．免疫组织化学法检测ALG2蛋白在OSCC组织中的表达。

Figure 3 Immunohistochemical expression of ALG2 protein in OSCC tissues and paracancerous normal tissues

表3 ALG2在OSCC组织中的表达与患者临床病理特征的相关性

Table 3 The relationship between the expression of ALG2 in OSCC tissues and the clinicopathological features of OSCC patients

临床病理特征	n(%)	ALG2的表达例数		P值
临床病理特征	n(%)	低	高	P值
年龄/岁
<60	97(75.8)	24	73	0.635
≥60	31(24.2)	9	22	0.635
性别
男	71(55.5)	22	49	0.133
女	57(44.5)	11	46	0.133
吸烟史
有	77(60.2)	24	53	0.087
无	51(39.8)	9	42	0.087
饮酒史
有	73(57.0)	20	53	0.630
无	55(43.0)	23	42	0.630
肿瘤位置
舌	36(28.1)	6	30	0.140
其他	92(71.9)	27	65	0.140
T分期
T1	34(26.6)	10	24	0.030
T2	48(37.5)	19	29
T3	31(24.2)	4	27
T4	15(11.7)	3	12
临床分期
Ⅰ	25(19.5)	12	13	0.081
Ⅱ	45(35.2)	14	31
Ⅲ	35(27.3)	15	20
Ⅳ	23(18.0)	9	14
淋巴结转移
无	54(42.2)	20	34	0.013
有	74(57.8)	13	61	0.013
组织分化
高	71(55.5)	17	54
中	32(25.0)	7	25	0.418
低	25(19.5)	9	16

图4 ALG2的表达水平对OSCC患者生存率的影响 A．ALG2表达水平与OSCC患者总体生存率的关系；B．ALG2表达水平与OSCC患者无疾病生存率的关系；C．ALG2表达水平与OSCC患者无进展生存率之间的关系；D．Kaplan-Meier法分析ALG2表达水平与OSCC患者总体生存率之间的关系。

Figure 4 Effect of ALG2 expression level on the survival of OSCC patients

表4 OSCC患者总体生存率的单因素和多因素分析

Table 4 Univariate analysis and multivariate analysis of prognostic factors in OSCC patients

	单因素分析		P值	多因素分析		P值
	HR	95%CI	P值	HR	95%CI	P值
年龄	0.998	0.969~1.028	0.903
性别	1.597	0.848~3.005	0.147
抽烟史	1.560	0.844~2.883	0.156
饮酒史	0.905	0.479~1.710	0.758
肿瘤位置	0.612	0.308~1.127	0.162
T分期	1.717	0.503~3.020	0.023	1.341	0.868~1.972	0.084
临床分期	1.801	0.968~3.321	0.076
淋巴结转移	0.613	0.419~0.897	0.012	0.593	0.397~0.885	0.035
组织分化	1.857	0.818~4.214	0.139
ALG2表达水平	2.531	1.042~3.701	0.011	2.615	1.713~3.581	0.009

图5 TCGA数据库分析ALG2对OSCC的诊断价值

Figure 5 The diagnostic value of ALG2 in OSCC were detected in TCGA database

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