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:

Objective To 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. Methods A 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. Results The 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 （all P<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 （all P<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 （all P<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）. Conclusion Compared 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