食管癌患者血清miR-497、miR-383水平及临床意义

摘要/Abstract

摘要：

目的观察食管癌患者血清miR-497、miR-383水平，并分析其对食管癌的临床意义。方法收集2018年7月—2020年2月协和武汉红十字会医院收治的食管癌患者作为食管癌组（n=96），并根据随访结果分为复发组（n=29）和未复发组（n=67），对照组为同期在本院进行体检的健康者（n=83），良性病变组为同期在本院就诊的食管良性病变患者（n=78）。采用实时荧光定量PCR对各组血清miR-497、miR-383水平进行检测；采用Pearson相关分析探讨食管癌患者血清miR-497和miR-383水平的相关性；分析食管癌患者血清miR-497、miR-383水平与临床病理特征的关系；绘制受试者操作特征（ROC）曲线分析血清miR-497、miR-383以及二者联合预测食管癌患者预后的效能。结果对照组、良性病变组以及食管癌组血清miR-497水平分别为1.01±0.18、0.86±0.15、0.77±0.14，血清miR-383水平分别为1.02±0.21、0.95±0.15、0.84±0.15，差异均有统计学意义（F=52.59，P<0.001；F=25.12，P<0.001）；3组血清miR-497、miR-383水平两两比较，差异均有统计学意义（均P<0.05）。Pearson相关分析显示，食管癌患者血清miR-497与miR-383水平呈正相关（r=0.46，P<0.001）。不同肿瘤直径（t=6.58，P<0.001；t=5.06，P<0.001）、淋巴结转移（t=5.55，P<0.001；t=4.63，P<0.001）、TNM分期（t=5.00，P<0.001；t=2.75，P<0.001）食管癌患者的血清miR-497、miR-383水平差异均具有统计学意义。未复发组血清miR-497（0.83±0.15比0.62±0.11，t=6.78，P<0.001）、miR-383（0.91±0.16比0.67±0.13，t=7.12，P<0.001）水平均高于复发组。ROC曲线分析显示，血清miR-497预测食管癌预后情况的临界值为0.72，敏感性为68.97%，特异性为68.66%，曲线下面积（AUC）为0.756；血清miR-383预测食管癌预后情况的临界值为0.84，敏感性为82.76%，特异性为67.16%，AUC为0.827；二者联合预测的敏感性为79.31%，特异性为85.07%，AUC为0.899；与血清miR-497（Z=3.31，P=0.001）、miR-383（Z=2.51，P=0.012）单独预测时的AUC相比，二者联合预测的效果更好。结论食管癌患者血清miR-497、miR-383水平较健康者及良性病变患者降低，与肿瘤直径、淋巴结转移、TNM分期及预后有关，二者联合检测对食管癌预后具有一定的预测价值。

关键词:食管肿瘤,预后,miR-497,miR-383

Abstract:

ObjectiveTo observe the serum levels of miR-497 and miR-383 in patients with esophageal cancer， and to analyze the clinical significance for esophageal cancer.MethodsEsophageal cancer patients admitted to Union Wuhan Red Cross Hospital from July 2018 to February 2020 were collected as the esophageal cancer group （n=96）， which were divided into a recurrence group （n=29） and a non recurrence group （n=67） based on follow-up results. The control group included healthy individuals who underwent physical examinations at this hospital during the corresponding period （n=83）， and the benign lesion group included patients with benign esophageal lesions who underwent treatment at same hospital during the corresponding period （n=78）. Real time fluorogenic quantitative PCR was applied to detect serum levels of miR-497 and miR-383 in each group； Pearson method was applied to analyze the correlation between serum levels of miR-497 and miR-383 in esophageal cancer patients； Relationship between serum levels of miR-497， miR-383 and clinical pathological characteristics in esophageal cancer patients was analyzed； Receiver operator characteristic （ROC） curve was plotted to analyze the efficacy of serum miR-497， miR-383， and their combination in predicting the prognosis of esophageal cancer patients.ResultsThe serum miR-497 levels in the control group， benign lesion group and the esophageal cancer group were 1.01±0.18， 0.86±0.15， 0.77±0.14， respectively， and the serum miR-383 levels were 1.02±0.21， 0.95±0.15， 0.84±0.15， respectively， with statistically significant differences （F=52.59，P<0.001；F=25.12，P<0.001）； There were statistically significant differences in serum miR-497 and miR-383 levels between any two of the three groups （allP<0.05）. Pearson correlation analysis reveled that serum miR-497 level was positively correlated with miR-383 level in esophageal cancer patients （r=0.46，P<0.001）. There were statistically significant differences in serum miR-497 and miR-383 levels among esophageal cancer patients with different tumor diameters （t=6.58，P<0.001；t=5.06，P<0.001）， lymph node metastases （t=5.55，P<0.001；t=4.63，P<0.001） and TNM stages （t=5.00，P<0.001；t=2.75，P<0.001）. The serum miR-497 （0.83±0.15vs.0.62±0.11，t=6.78，P<0.001） and miR-383 （0.91±0.16vs.0.67±0.13，t=7.12，P<0.001） levels in the non recurrence group were both higher than those in the recurrence group. ROC curve showed that the critical value of serum miR-497 for predicting the prognostic situation of esophageal cancer was 0.72， with a sensitivity of 68.97%， a specificity of 68.66%， and an area under the curve （AUC） of 0.756； The critical value of serum miR-383 was 0.84， with a sensitivity of 82.76%， a specificity of 67.16%， and an AUC of 0.827； The sensitivity of the combination of the two was 79.31%， the specificity was 85.07%， and the AUC was 0.899； The combination of the two had a better prediction effect than that of serum miR-497 （Z=3.31，P=0.001） and miR-383 （Z=2.51，P=0.012） alone.ConclusionThe serum levels of miR-497 and miR-383 in patients with esophageal cancer are lower than those in healthy individuals and patients with benign lesions， which are related to tumor diameter， lymph node metastasis， TNM stage， and prognosis. The combined detection of the two has certain predictive value for the prognosis of esophageal cancer.

Key words:Esophageal neoplasms,Prognosis,miR-497,miR-383

万芳, 杨钢, 李睿, 万启晶. 食管癌患者血清miR-497、miR-383水平及临床意义[J]. 国际肿瘤学杂志, 2024, 51(4): 204-209.

Wan Fang, Yang Gang, Li Rui, Wan Qijing. Expression levels and clinical significance of serum miR-497 and miR-383 in patients with esophageal cancer[J]. Journal of International Oncology, 2024, 51(4): 204-209.

图/表7

基因	正向引物	反向引物
miR-497	5’-CATACCTGACTGTGTTGCTAAA-3’	5’-CTTTTGAGTGTTGGTGATTTGG-3’
miR-383	5’-TCAGAAGGTGATTGTGGC-3’	5’-GAACATGTCTGCGTATCTC-3’
U6	5’-CTCGCTTCGGCAGCACA-3’	5’-AACGCTTCACGAATTTGCGT-3’

表1

一般资料	对照组（n=83）	良性病变组（n=78）	食管癌组（n=96）	χ²/t值	P值
性别
男	49（59.04）	46（58.97）	58（60.42）	0.05	0.975
女	34（40.96）	32（41.03）	38（39.58）
年龄（岁）	59.36±6.42	58.39±6.71	59.62±6.37	0.83	0.438
体质量指数（kg/m²）	22.37±3.13	23.05±3.99	22.96±3.52	0.90	0.409
收缩压（mmHg）	123.51±14.22	122.63±13.62	123.28±13.86	0.09	0.917
舒张压（mmHg）	76.85±8.72	77.61±9.16	76.19±8.31	0.57	0.565

表2

组别	miR-497	miR-383
对照组（n=83）	1.01±0.18	1.02±0.21
良性病变组（n=78）	0.86±0.15^a	0.95±0.15^a
食管癌组（n=96）	0.77±0.14^ab	0.84±0.15^ab
F值	52.59	25.12
P值	<0.001	<0.001

表3

表4

96例食管癌患者血清miR-497、miR-383水平与临床病理特征的关系（$\bar{x}±s$）"

临床病理特征	例数	miR-497	t值	P值	miR-383	t值	P值
肿瘤直径（cm）
≥4	51	0.68±0.11	6.58	<0.001	0.76±0.14	5.06	<0.001
<4	45	0.87±0.17	6.58	<0.001	0.92±0.17	5.06	<0.001
病理类型
腺癌	34	0.74±0.13	1.37	0.173	0.81±0.14	1.22	0.224
鳞状细胞癌	62	0.78±0.14	1.37	0.173	0.85±0.16	1.22	0.224
组织分化程度
低分化	56	0.77±0.15	0.35	0.728	0.85±0.15	0.97	0.336
中高分化	40	0.76±0.12	0.35	0.728	0.82±0.15	0.97	0.336
淋巴结转移
有	23	0.63±0.12	5.55	<0.001	0.71±0.13	4.63	<0.001
无	73	0.81±0.14	5.55	<0.001	0.88±0.16	4.63	<0.001
TNM分期
Ⅰ~Ⅱ期	59	0.83±0.16	5.00	<0.001	0.87±0.17	2.75	<0.001
Ⅲ~Ⅳ期	37	0.68±0.11	5.00	<0.001	0.78±0.13	2.75	<0.001

表4

组别	miR-497	miR-383
复发组（n=29）	0.62±0.11	0.67±0.13
未复发组（n=67）	0.83±0.15	0.91±0.16
t值	6.78	7.12
P值	<0.001	<0.001

表5

图1

变量	Youden指数	截断值	敏感性（%）	特异性（%）	AUC	95%CI	P值
miR-497	0.376	0.72	68.97	68.66	0.756	0.657~0.838	<0.001
miR-383	0.499	0.84	82.76	67.16	0.827	0.736~0.896	<0.001
二者联合	0.644	-	79.31	85.07	0.899	0.821~0.951	<0.001

表6

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