经阴道超声弹性成像联合血清miR-144-3p、CMTM6在宫颈癌前病变和宫颈癌中的鉴别诊断价值

摘要/Abstract

摘要：

目的探究经阴道超声弹性成像联合血清微RNA-144-3p（miR-144-3p）、趋化素样因子MARVEL跨膜结构域蛋白6（CMTM6）在宫颈癌前病变和宫颈癌中的鉴别诊断价值。方法收集2021年9月至2023年9月山西省妇幼保健院收治的110例宫颈癌患者作为宫颈癌组，同时选择本院收治的105例宫颈上皮内瘤变（CIN）患者作为CIN组，另选取同期在本院健康体检者100例作为对照组。采用彩色多普勒超声诊断仪对所有研究对象进行经阴道超声弹性成像检查；实时荧光定量PCR法测定血清miR-144-3p水平；酶联免疫法检测血清CMTM6水平；采用受试者操作特征（ROC）曲线分析超声弹性成像评分联合血清miR-144-3p、CMTM6水平对宫颈癌前病变和宫颈癌的鉴别诊断价值。结果对照组、CIN组和宫颈癌组超声弹性成像评分分别为（1.45±0.22）、（3.16±0.34）、（3.62±0.41）分，差异有统计学意义（F=1 197.26，P<0.001）；miR-144-3p水平分别为1.02±0.12、0.72±0.13、0.57±0.12，差异有统计学意义（F=357.65，P<0.001）；CMTM6水平分别为（15.89±3.46）、（25.82±6.59）、（34.73±8.52）pg/ml，差异有统计学意义（F=213.05，P<0.001）；进一步两两比较发现，对照组、CIN组和宫颈癌组超声弹性成像评分及CMTM6水平依次升高，miR-144-3p水平依次降低（均P<0.05）。CINⅠ级（n=21）、CINⅡ级（n=44）、CINⅢ级（n=40）患者的超声弹性成像评分分别为（2.86±0.30）、（3.16±0.33）、（3.32±0.35）分，差异有统计学意义（F=13.20，P<0.001）；miR-144-3p水平分别为0.80±0.09、0.73±0.08、0.67±0.07，差异有统计学意义（F=19.37，P<0.001）；CMTM6水平分别为（20.35±2.58）、（25.76±2.71）、（28.76±2.96）pg/ml，差异有统计学意义（F=62.84，P<0.001）；进一步两两比较发现，随着CIN分级（Ⅰ级、Ⅱ级和Ⅲ级）的升高，CIN患者超声弹性成像评分及CMTM6水平依次升高，miR-144-3p水平依次降低（均P<0.05）。国际妇产科联盟（FIGO）分期为Ⅰ期（n=36）、Ⅱ期（n=42）、Ⅲ~Ⅳ期（n=32）患者的超声弹性成像评分分别为（3.39±0.35）、（3.65±0.38）、（3.84±0.40）分，差异有统计学意义（F=12.31，P<0.001）； miR-144-3p水平分别为0.64±0.07、0.58±0.06、0.48±0.06，差异有统计学意义（F=54.65，P<0.001）；CMTM6水平分别为（31.58±3.39）、（34.62±3.75）、（38.42±4.02）pg/ml，差异有统计学意义（F=28.69，P<0.001）；进一步两两比较发现，随着宫颈癌FIGO分期（Ⅰ期、Ⅱ期、Ⅲ~Ⅳ期）的升高，宫颈癌患者超声弹性成像评分及CMTM6水平均依次升高，miR-144-3p水平依次降低（均P<0.05）。ROC曲线分析显示，超声弹性成像评分、miR-144-3p，CMTM6水平和三者联合鉴别诊断CIN和宫颈癌的曲线下面积（AUC）分别为0.781、0.793、0.818、0.930，三者联合的鉴别诊断价值优于单独诊断（Z=6.18，P<0.001；Z=4.79，P=0.026；Z=4.49，P=0.031）。结论宫颈癌患者经阴道超声弹性成像评分与CIN组、对照组相比升高，血清miR-144-3p水平降低，CMTM6水平升高，三者联合检测对CIN和宫颈癌有一定的鉴别诊断价值。

关键词:宫颈肿瘤,宫颈癌前病变,超声弹性成像,微RNAs,趋化素样因子MARVEL跨膜结构域蛋白6

Abstract:

ObjectiveTo explore the differential diagnostic value of transvaginal ultrasound elastography combined with serum microRNA-144-3p （miR-144-3p） and CKLF-like MARVEL transmembrane domain containing protein 6 （CMTM6） for cervical precancerous lesions and cervical cancer.MethodsA total of 110 patients with cervical cancer admitted to Shanxi Women and Children Hospital from September 2021 to September 2023 were collected as cervical cancer group，105 patients with cervical intraepithelial neoplasia （CIN） admitted to our hospital were selected as the CIN group，another 100 healthy individuals who underwent physical examinations in hospital during the same period were regarded as the control group. Color Doppler ultrasound diagnostic instrument was applied to all research objects for transvaginal ultrasound elastography examination，real-time fluorescence quantitative PCR was applied to measure serum miR-144-3p level，enzyme-linked immunosorbent assay was applied to detect serum CMTM6 level，and receiver operator characteristic （ROC） curve was applied to analyze the significance of differential diagnosis of ultrasound elastography score combined with serum miR-144-3p and CMTM6 levels for cervical precancerous lesions and cervical cancer.ResultsThe ultrasound elastography scores of control group，CIN group and cervical cancer group were 1.45±0.22，3.16±0.34 and 3.62±0.41，respectively，with a statistically significant difference （F=1 197.26，P<0.001）. The levels of miR-144-3p were 1.02±0.12，0.72±0.13，0.57±0.12，respectively，with a statistically significant difference （F=357.65，P<0.001）. The CMTM6 levels were （15.89±3.46），（25.82±6.59） and （34.73±8.52） pg/ml，respectively，with a statistically significant difference （F=213.05，P<0.001）. Further pairwise comparison showed that the elastography scores and CMTM6 levels in the control group，CIN group and cervical cancer group were increased successively，while the levels of miR-144-3p were decreased successively （allP<0.05）. The ultrasound elastography scores of CIN Ⅰ grade （n=21），CIN Ⅱ grade （n=44） and CIN Ⅲ grade （n=40） patients were 2.86±0.30，3.16±0.33 and 3.32±0.35，respectively，with a statistically significant difference （F=13.20，P<0.001）. The levels of miR-144-3p were 0.80±0.09，0.73±0.08，0.67±0.07，respectively，with a statistically significant difference （F=19.37，P<0.001）. CMTM6 levels were （20.35±2.58），（25.76±2.71） and （28.76±2.96） pg/ml，respectively，with a statistically significant difference （F=62.84，P<0.001）. Further pairwise comparison showed that with the CIN grade （levels Ⅰ，Ⅱ and Ⅲ） increased，the ultrasound elastography scores and CMTM6 levels of CIN patients increased in turn，while the levels of miR-144-3p decreased in turn （allP<0.05）. The ultrasound elastography scores of International Federation of Gynecology and Obstetrics （FIGO） stage Ⅰ （n=36），Ⅱ （n=42） and Ⅲ-Ⅳ （n=32） patients were 3.39±0.35，3.65±0.38 and 3.84±0.40，respectively，with a statistically significant difference （F=12.31，P<0.001）. The levels of miR-144-3p were 0.64±0.07，0.58±0.06 and 0.48±0.06，respectively，with a statistically significant difference （F=54.65，P<0.001）. CMTM6 levels were （31.58±3.39），（34.62±3.75），（38.42±4.02） pg/ml，respectively，with a statistically significant difference （F=28.69，P<0.001）. Further pairwise comparison showed that with the increase of FIGO stage （stage Ⅰ，stage Ⅱ，stage Ⅲ-Ⅳ） of cervical cancer，the ultrasound elastography scores and CMTM6 levesl of cervical cancer patients increased in turn，and the levels of miR-144-3p decreased in turn （allP<0.05）. ROC curve analysis showed that the area under the curve （AUC） of ultrasound elastography score，miR-144-3p，CMTM6 levels，and the above three combined for differential diagnosis of CIN and cervical cancer was 0.781，0.793，0.818，and 0.930，respectively，the combined differential diagnostic value of the three was better than that of single diagnosis （Z=6.18，P<0.001；Z=4.79，P=0.026；Z=4.49，P=0.031）.ConclusionCompared with CIN group and control group，the transvaginal ultrasound elastography score increases，the serum miR-144-3p level decreases and the CMTM6 level increases in cervical cancer patients. The combination of the three has certain differential diagnostic value for CIN and cervical cancer.

Key words:Uterine cervical neoplasms,Cervical precancerous lesions,Ultrasound elastography,MicroRNAs,CKLF-like MARVEL transmembrane domain containing protein 6

王燕. 经阴道超声弹性成像联合血清miR-144-3p、CMTM6在宫颈癌前病变和宫颈癌中的鉴别诊断价值[J]. 国际肿瘤学杂志, 2024, 51(8): 504-509.

Wang Yan. Differential diagnostic value of transvaginal ultrasound elastography combined with serum miR-144-3p，CMTM6 for cervical precancerous lesions and cervical cancer[J]. Journal of International Oncology, 2024, 51(8): 504-509.

图/表6

基因	正向引物5'-3'	反向引物5'-3'
miR-144-3p	CTCTATCCAAAACAGGCCGC	TTTACATCCCCAAGGCCCAT
U6	CTCGCTTCGGCAGCACA	AACGCTTCACGAATTTGCGT

表1

组别	超声弹性成像评分（分）	miR-144-3p	CMTM6 （pg/ml）
对照组（n=100）	1.45±0.22	1.02±0.12	15.89±3.46
CIN组（n=105）	3.16±0.34^a	0.72±0.13^a	25.82±6.59^a
宫颈癌组（n=110）	3.62±0.41^ab	0.57±0.12^ab	34.73±8.52^ab
F值	1 197.26	357.65	213.05
P值	<0.001	<0.001	<0.001

表2

分级	超声弹性成像评分（分）	miR-144-3p	CMTM6 （pg/ml）
CIN Ⅰ级（n=21）	2.86±0.30	0.80±0.09	20.35±2.58
CIN Ⅱ级（n=44）	3.16±0.33^a	0.73±0.08^a	25.76±2.71^a
CIN Ⅲ级（n=40）	3.32±0.35^ab	0.67±0.07^ab	28.76±2.96^ab
F值	13.20	19.37	62.84
P值	<0.001	<0.001	<0.001

表3

FIGO分期	超声弹性成像评分（分）	miR-144-3p	CMTM6 （pg/ml）
Ⅰ期（n=36）	3.39±0.35	0.64±0.07	31.58±3.39
Ⅱ期（n=42）	3.65±0.38^a	0.58±0.06^a	34.62±3.75^a
Ⅲ~Ⅳ期（n=32）	3.84±0.40^ab	0.48±0.06^ab	38.42±4.02^ab
F值	12.31	54.65	28.69
P值	<0.001	<0.001	<0.001

表4

图1

项目	敏感性（%）	特异性（%）	最佳截断值	AUC	95%CI
超声弹性成像评分	61.82	87.62	3.00分	0.78	0.72~0.84
miR-144-3p	81.82	68.57	0.66	0.79	0.73~0.85
CMTM6	73.64	81.90	30.40 pg/ml	0.82	0.76~0.87
三者联合	87.27	85.71		0.93	0.89~0.96

表5

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