早期结直肠癌患者外周血单个核细胞中TOP2A、ERBB2的水平及其诊断价值

doi:10.3760/cma.j.cn371439-20230724-00135

摘要/Abstract

摘要：

目的探究拓扑异构酶Ⅱα（TOP2A）、人表皮生长因子受体2（ERBB2）在早期结直肠癌（CRC）中的水平及其诊断价值。方法选取2019年1月至2022年4月石家庄市中医院收治的93例早期CRC患者为研究对象（CRC组），选取同期健康体检者93例作为健康组，同期诊治的结直肠息肉患者93例作为结直肠息肉组。检测并比较各组受试对象外周血单个核细胞（PBMC）中TOP2A、ERBB2 mRNA以及血清癌胚抗原（CEA）水平。采用受试者操作特征（ROC）曲线评估TOP2A、ERBB2 mRNA及血清CEA水平诊断早期CRC的价值。分析TOP2A、ERBB2 mRNA水平与早期CRC患者临床病理特征的关系。结果健康组、结直肠息肉组、CRC组PBMC中TOP2A（1.04±0.35比1.72±0.57比2.83±0.71，F=246.73，P<0.001）、ERBB2 mRNA（1.01±0.34比1.64±0.55比2.75±0.71，F=234.80，P<0.001）及血清CEA水平（1.29±0.52比1.93±0.64比3.17±0.81，F=190.78，P<0.001）差异均有统计学意义。与健康组、结直肠息肉组相比，CRC组PBMC中TOP2A、ERBB2 mRNA及血清CEA水平均显著升高（均P<0.05）；与健康组相比，结直肠息肉组PBMC中TOP2A、ERBB2 mRNA及血清CEA水平均升高（均P<0.05）。ROC曲线分析显示，PBMC中TOP2A、ERBB2 mRNA及血清CEA水平诊断早期CRC的曲线下面积（AUC）分别为0.85、0.85、0.84，三者联合诊断早期CRC的AUC为0.96，大于TOP2A、ERBB2、CEA单独诊断（Z=2.92，P=0.004；Z=3.16，P=0.002；Z=2.86，P=0.005）。三者联合诊断早期CRC的敏感性为94.64%，特异性为85.96%。不同分化程度早期CRC患者PBMC中TOP2A、ERBB2 mRNA水平差异有统计学意义（χ²=6.21，P=0.013；χ²=10.49，P=0.001）。结论 CRC患者PBMC中TOP2A、ERBB2 mRNA水平较高，PBMC中TOP2A、ERBB2 mRNA水平联合血清CEA水平有助于临床诊断早期CRC。

关键词: 结直肠肿瘤, DNA拓扑异构酶类，Ⅱ型, 基因，erbB-2

Abstract:

Objective To investigate the levels and diagnostic value of topoisomerase Ⅱα （TOP2A） and human epidermal growth factor receptor 2 （ERBB2） in early colorectal cancer （CRC）. Methods Ninty-three early CRC patients （CRC group） admitted to Shijiazhuang Hospital of Traditional Chinese Medicine were selected for the study from January 2019 to April 2022， and 93 healthy subjects during the same period were selected as the healthy group， and 93 colorectal polyps patients diagnosed and treated in the same period were selected as the colorectal polyp group. TOP2A and ERBB2 mRNA levels in peripheral blood mononuclear cell （PBMC） and serum carcinoembryonic antigen （CEA） level were detected and compared in each group. The value of TOP2A， ERBB2 mRNA and serum CEA level in the diagnosis of early CRC were evaluated by using receiver operating characteristic（ROC） curve. The relationship between TOP2A and ERBB2 levels and clinicopathological features of early CRC patients was analyzed. Results There were statistically significant differences in the PBMC TOP2A （1.04±0.35 vs. 1.72±0.57 vs. 2.83±0.71， F=246.73， P<0.001）， ERBB2 mRNA （1.01±0.34 vs. 1.64±0.55 vs. 2.75±0.71， F=234.80， P<0.001） levels and serum CEA levels （1.29±0.52 vs. 1.93±0.64 vs. 3.17±0.81， F=190.78， P<0.001） in healthy group， colorectal polyp group and CRC group. Compared with the healthy group and colorectal polyp group， the levels of TOP2A and ERBB2 mRNA in PBMC and serum CEA level in CRC group were significantly increased （all P<0.05）； Compared with the healthy group， the levels of TOP2A and ERBB2 mRNA in PBMC and serum CEA level in the colorectal polyp group were increased （all P<0.05）. The ROC curve showed that the area under curve （AUC） of TOP2A and ERBB2 mRNA levels in PBMC and serum CEA level for the diagnosis of early CRC were 0.85， 0.85 and 0.84， respectively， and the AUC for the combined diagnosis of early CRC was 0.96， which was higher than that of TOP2A， ERBB2 and CEA alone （Z=2.92， P=0.004； Z=3.16， P=0.002； Z=2.86， P=0.005）. The combination of the three diagnosed early CRC with a sensitivity of 94.64% and a specificity of 85.96%. There were statistically significant differences in PBMC TOP2A and ERBB2 mRNA levels in early CRC patients with different differentiation degrees （χ²=6.21， P=0.013； χ²=10.49， P=0.001）. Conclusion The expression levels of TOP2A， ERBB2 mRNA in PBMC in CRC patients are higher. The combination of TOP2A， ERBB2 mRNA levels in PBMC and serum CEA level may be more helpful for clinical diagnosis of early CRC.

Key words: Colorectal neoplasms, DNA topoisomerases， type Ⅱ, Genes， erbB-2

刘玉杰, 赵志强, 王子琤. 早期结直肠癌患者外周血单个核细胞中TOP2A、ERBB2的水平及其诊断价值[J]. 国际肿瘤学杂志, 2023, 50(12): 717-722.

Liu Yujie, Zhao Zhiqiang, Wang Zicheng. Levels and diagnostic value of TOP2A and ERBB2 in peripheral blood mononuclear cells of patients with early colorectal cancer[J]. Journal of International Oncology, 2023, 50(12): 717-722.

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组别	性别（男/女）	年龄（岁）
健康组（n=93）	52/41	53.72±9.44
结直肠息肉组（n=93）	54/39	54.05±9.71
CRC组（n=93）	50/43	53.24±9.35
χ²/F值	0.35	0.17
P值	0.840	0.843

组别	TOP2A mRNA	ERBB2 mRNA	CEA（ng/ml）
健康组（n=93）	1.04±0.35	1.01±0.34	1.29±0.52
结直肠息肉组（n=93）	1.72±0.57^a	1.64±0.55^a	1.93±0.64^a
CRC组（n=93）	2.83±0.71^ab	2.75±0.71^ab	3.17±0.81^ab
F值	246.73	234.80	190.78
P值	<0.001	<0.001	<0.001

指标	最佳截断值	AUC	95%CI	敏感性（%）	特异性（%）	约登指数
TOP2A	2.23	0.85	0.72~0.92	81.71	87.09	0.69
ERBB2	2.15	0.85	0.78~0.92	74.16	89.24	0.63
CEA	2.77 ng/ml	0.84	0.75~0.92	74.21	88.19	0.62
三者联合	-	0.96	0.94~0.99	94.64	85.96	0.81

临床病理特征	TOP2A				ERBB2
临床病理特征	低水平组（n=46）	高水平组（n=47）	χ²值	P值	低水平组（n=48）	高水平组（n=45）	χ²值	P值
性别
男	24（52.17）	26（55.32）	0.09	0.761	28（58.33）	22（48.89）	0.83	0.361
女	22（47.83）	21（44.68）	0.09	0.761	20（41.67）	23（51.11）	0.83	0.361
年龄（岁）
<55	20（43.48）	19（40.43）	0.09	0.765	18（37.50）	21（46.67）	0.80	0.371
≥55	26（56.52）	28（59.57）	0.09	0.765	30（62.50）	24（53.33）	0.80	0.371
肿瘤大小（mm）
<15	23（50.00）	22（46.81）	0.10	0.758	26（54.17）	19（42.22）	1.33	0.249
15~30	23（50.00）	25（53.19）	0.10	0.758	22（45.83）	26（57.78）	1.33	0.249
肿瘤位置
直肠	19（41.30）	18（38.30）	1.80	0.406	21（43.75）	16（35.56）
右半结肠	14（30.43）	20（42.55）			16（33.33）	18（40.00）	0.70	0.706
左半结肠	13（28.26）	9（19.15）			11（22.92）	11（24.44）
分化程度
低分化	3（6.52）	12（25.53）	6.21	0.013	2（4.17）	13（28.89）	10.49	0.001
中、高分化	43（93.48）	35（74.47）	6.21	0.013	46（95.83）	32（71.11）	10.49	0.001