血清CA125、HE4及基于二者的ROMA、CPH-I在卵巢腫瘤良惡性鑒別診斷中的應(yīng)用價值

陳詠寧　張雅迪　陳莉　李嬋媛　吳煥　龔時鵬

[摘要] 目的 對比分析血清糖類抗原125（CA125）和人附睪上皮分泌蛋白4（HE4）及基于二者計算的卵巢惡性腫瘤風險模型（ROMA）、哥本哈根指數(shù)（CPH-I）在卵巢良惡性腫瘤鑒別診斷中的應(yīng)用價值。 方法 回顧性分析2014年9月～2016年11月于南方醫(yī)科大學南方醫(yī)院婦產(chǎn)科就診的719例卵巢腫瘤患者的臨床資料。根據(jù)預(yù)后的差別將患者分為少見組織病理學類型卵巢惡性腫瘤（LCOHs）組（92例），非少見組織病理學類型卵巢惡性腫瘤（Non-LCOHs）組（96例），良性腫瘤（BOTs）組（531例）。采用ROC曲線計算CA125、HE4、ROMA、CPH-I的AUC、靈敏度、特異度，比較其鑒別LCOHs、Non-LCOHs和BOTs的效能大小。 結(jié)果 LCOHs組早期比例較高（80.4%），Non-LCOHs組以晚期為主（77.1%）（P < 0.01）;各組年齡、已絕經(jīng)女性比例、CA125、HE4、ROMA、CPH-I大小排序為：Non-LCOHs組>LCOHs組>BOTs組（P < 0.01）;在鑒別Non-LCOHs和BOTs時，ROMA、CPH-I、HE4（0.969、0.968、0.968）的AUC均大于CA125（0.935）;靈敏度排序：CPH-I>ROMA>CA125>HE4（93.8%、92.7%、90.6%、88.5%）。在鑒別LCOHs和BOTs時，亦觀察到相似的AUC趨勢（0.735、0.739、0.736和0.642）;ROMA、CA125靈敏度大于CPH-I、HE4（44.6%、35.9%和32.6%，32.6%）。特異度排序：CPH-I>HE4>ROMA>CA125（94.7%、93.6%、87.6%、83.6%）。 結(jié)論 HE4、ROMA、CPH-I三者總體診斷效能相當，均優(yōu)于CA125。在預(yù)測Non-LCOHs時，ROMA和CPH-I優(yōu)于CA125，CPH-I稍占優(yōu)勢且更為簡便實用，三者均優(yōu)于HE4。在篩檢出BOTs方面，CPH-I和HE4優(yōu)于ROMA，三者有效彌補CA125特異性差的缺陷。CA125、HE4、ROMA、CPH-I用于發(fā)現(xiàn)LCOHs時漏診率仍較高，還需進一步探索新的鑒別手段。

[關(guān)鍵詞] 卵巢腫瘤;CA125;HE4;ROMA;CPH-I;鑒別診斷

[中圖分類號] R737.31? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-7210（2019）06（b）-0009-05

Application value of serum CA125， HE4 and ROMA and CPH-I based on them in differential diagnosis of ovarian tumors

CHEN Yongning1? ?ZHANG Yadi1? ?CHEN Li2? ?LI Chanyuan1? ?WU Huan3? ?GONG Shipeng1

1.Department of Obstetrics and Gynecology， Nanfang Hospital， Southern Medical University， Guangdong Province， Guangzhou? ? 510515， China; 2.PET Center， Nanfang Hospital， Southern Medical University， Guangdong Province， Guangzhou? ? 510515， China; 3.Department of Obstetrics and Gynecology， the Second Affiliated Hospital， Chongqing Medical University， Chongqing? ?400010， China

[Abstract] Objective To compare diagnostic value of carbohydrate antigen 125 （CA125）， human epididymis protein 4 （HE4） and on which risk of ovarian malignancy algorithm （ROMA）， Copenhagen index （CPH-I） based in differentiating malignant from benign ovarian tumors. Methods Clinical data of 719 patients with ovarian tumors， who visited Department of Obstetrics and Gynecology of Nanfang Hospital， Southern Medical University， from September 2014 to November 2016 were analyzed retrospectively. According to different prognosis， patients were divided into 92 cases of less common ovarian histopathologies （LCOHs） group， 96 cases of non-less common ovarian histopathologies （Non-LCOHs） group， 531 cases of benign ovarian tumors （BOTs） group. ROC curve were used for calculating AUC， sensitivities and specificities， so as to compare diagnostic value of CA125， HE4， ROMA and CPH-I in differentiating malignant from benign ovarian tumors. Results Among ovarian cancer， 77.1% patients in non-LCOHs group were mainly staged advanced， while those in LCOHs group， 80.4% were mainly early stage， the differences were statistically significant （P < 0.01）. The age， rate of postmenstrual cases and levels of serum CA125， HE4， ROMA， CPH-I in Non-LCOHs group were higher， followed by LCOHs group and BOTs group respectively， the differences were statistically significant （P < 0.01）. In differentiating Non-LCOHs from BOTs patients， AUC of CPH-I， ROMA and HE4 were both higher than CA125 （0.969， 0.968， 0.968 and 0.935）， and CPH-I made highest sensitivity， followed by ROMA， CA125 and HE4 （93.8%， 92.7%， 90.6% and 88.5%）. Similar AUC trend was observed in differentiating LCOHs from BOTs patients （0.735， 0.739， 0.736 and 0.642）， and sensitivity of ROMA was highest and followed by CPH-I， CA125 and HE4 （44.6%， 35.9%， 32.6% and 32.6%）. The specificity of CPH-I， HE4， ROMA was higher than CA125 （94.7%， 93.6%， 87.6% and 83.6%）. Conclusion HE4， ROMA， and CPH-I did the comparative performance in differentiating malignant from benign ovarian tumors and both are better than CA125. In terms of predicting Non-LCOHs patients， ROMA and CPH-I are superior to CA125， and CPH-I is slightly dominant and more convenient and practical than ROMA. Both of these models perform better than HE4. Furthermore， CPH-I and HE4 has better specificities for predicting benign ovarian diseases than ROMA and the former two index made up for shortcoming of weak specificity of CA125 effectively. However， the rate of missed diagnosis in LCOHs population is still staying at a high level and further researches for more effective differential diagnosis tools are needed.

[Key words] Ovarian neoplasms; CA125; HE4; ROMA; CPH-I; Differential diagnosis

多數(shù)卵巢癌被診斷時已屬晚期（70%～75%），5年生存率僅20%～30%[1]。而早期卵巢癌5年生存率高，Ⅰ期患者甚至高達90%～95%，因此提高早期診斷率將有助于改善預(yù)后[1-3]。

糖類抗原125（carbohydrate antigen 125，CA125）在Ⅲ～Ⅳ期卵巢癌中靈敏度可達80%～90%，但在Ⅰ期患者中僅50%，在婦科良性疾病、其他惡性腫瘤等也伴有CA125非特異性升高[3-4]。研究[5-8]表明，人附睪上皮分泌蛋白4（human epididymis protein 4，HE4）在上皮性卵巢癌（epithelial ovarian cancer，EOC）中高表達，在癌旁組織、婦科良性疾病組織中低甚至不表達，在不同類型EOC中表達水平也不同。