Diagnostic value of ROMA and CPH-I in early epithelial ovarian cancer
-
摘要:
目的 探讨卵巢恶性肿瘤风险算法(ROMA)和哥本哈根指数(CPH-I)在早期上皮性卵巢恶性肿瘤(EOC)中的诊断价值。 方法 选取2018年1月—2020年12月就诊于蚌埠医学院第一附属医院的139例上皮性卵巢肿瘤患者(其中早期EOC 52例,上皮性卵巢交界性肿瘤24例,上皮性卵巢良性肿瘤63例)进行回顾性研究,搜集入选者的年龄、绝经状态、血清人附睾蛋白4(HE4)和癌抗原125(CA125)值,计算ROMA和CPH-I值, 通过绘制曲线下面积(AUC)来衡量这些指标的诊断准确性,并计算CA125、HE4、ROMA和CPH-I在各个组别诊断中的灵敏度、特异度。 结果 在各个组别的对比中,CPH-I、ROMA、HE4的AUC均优于CA125。且组间比较结果显示,4种指标均为早期恶性组 > 交界性组 > 良性组,差异均有统计学意义(均P < 0.001)。在预测卵巢肿瘤良恶性时,CA125、ROMA较HE4和CPH-I具有更好的灵敏度(88.46%、92.31% vs. 82.69%、86.54%),而HE4和CPH-I在特异度上优于CA125、ROMA(93.65%、96.83% vs. 76.19%、90.48%)。再按照绝经状态分组后, 早期恶性组与良性组比较,绝经后患者ROMA、CPH-I的AUC、灵敏度、特异度均高于绝经前患者(0.995、0.992 vs. 0.905、0.935, 96.77%、96.77% vs. 85.71%、71.43%, 95.83%、95.83% vs. 87.18%、94.87%)。 结论 在早期EOC的诊断中,ROMA具有更好的灵敏度,而CPH-I特异度优于ROMA;ROMA、CPH-I在绝经后患者中具有更好的灵敏度及特异度。 -
关键词:
- 卵巢恶性肿瘤风险模型 /
- 哥本哈根指数 /
- 血清人附睾分泌蛋白4 /
- 糖类抗原125 /
- 卵巢上皮性肿瘤
Abstract:Objective To investigate the diagnostic value of risk of ovarian malignancy algorithm (ROMA) and Copenhagen index (CPH-I) in early epithelial ovarian cancer (EOC). Methods A total of 139 patients with epithelial ovarian tumour (including 52 patients with early EOC, 24 patients with epithelial ovarian borderline tumour and 63 patients with epithelial ovarian benign tumour) admitted to the First Affiliated Hospital of Bengbu Medical College from January 2018 to December 2020 were retrospectively studied. Age, menopausal status and serum HE4 and CA125 values were collected for ROMA and CPH-I. The diagnostic accuracy of these indicators was measured by plotting the area under the curve (AUC), and the sensitivity and specificity of CA125, HE4, ROMA and CPH-I for each group were calculated. Results The AUC of CPH-I, ROMA and HE4 was superior to that of CA125 in all groups. The Results of inter-group comparison showed that the four indexes were early malignant group>borderline group>benign group. The differences were statistically significant (P < 0.001). CA125 and ROMA were more sensitive than HE4 and CPH-I in predicting benign or malignant ovarian neoplasms (88.46%, 92.31% vs. 82.69%, 86.54%). HE4 and CPH-I were more specific than CA125 and ROMA (93.65%, 96.83% vs. 76.19%, 90.48%). After grouping according to menopausal status, in the comparison between the early malignant group and the benign group, post-menopausal ROMA and CPH-I had higher AUC, sensitivity and specificity than pre-menopausal ROMA (0.995, 0.992 vs. 0.905, 0.935; 96.77%, 96.77% vs. 85.71%, 71.43%; 95.83%, 95.83% vs. 87.18%, 94.87%). Conclusion ROMA is more sensitive to early EOC diagnosis, and CPH-I is more specific than ROMA. ROMA and CPH-I have high sensitivity and specificity in post-menopausal patients. -
表 1 3组卵巢肿瘤患者基本资料比较
组别 例数 年龄[M(P25, P75), 岁] 绝经状态[例(%)] 未绝经 已绝经 良性组 63 40.00(27.00,59.00) 39(61.9) 24(38.1) 交界性组 24 44.50(27.25,56.75) 15(62.5) 9(37.5) 早期恶性组 52 53.50(47.25,60.75) 21(40.4) 31(59.6) 统计量 12.446a 6.163b P值 0.002 0.046 注:a为H值,b为χ2值。 表 2 3组卵巢肿瘤患者CA125、HE4、ROMA、CPH-I比较[M(P25, P75)]
组别 例数 CA125(IU/mL) HE4(pmol/L) ROMA(%) CPH-I(%) 良性组 63 16.00(10.70,26.30) 44.30(39.20,56.30) 6.21(4.79,12.77) 0.97(0.54,2.33) 交界性组 24 53.05(28.98,73.93)a 98.40(49.95,167.90)a 32.18(7.57,58.06)a 6.82(1.61,20.70)a 早期恶性组 52 167.55(48.00,490.93)ab 244.95(108.75,542.01)ab 76.97(35.62,95.10)ab 57.87(10.84,93.54)ab H值 60.291 77.030 75.764 81.557 P值 < 0.001 < 0.001 < 0.001 < 0.001 注:与良性组比较,aP < 0.05;与交界性组比较,bP < 0.05。 表 3 4种指标的鉴别诊断价值
组别 AUC(95% CI) 灵敏度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) 早期恶性组与良性组 CA125 0.889(0.829~0.949) 88.46 76.19 75.41 88.89 HE4 0.949(0.904~0.993) 82.69 93.65 91.49 86.76 ROMA 0.944(0.897~0.991) 92.31 90.48 88.89 95.00 CPH-I 0.959(0.925~0.993) 86.54 96.83 93.75 89.55 早期恶性组与交界性组 CA125 0.765(0.662~0.869) 88.46 76.19 74.19 57.14 HE4 0.769(0.665~0.874) 82.69 95.24 76.79 55.00 ROMA 0.776(0.674~0.878) 92.31 90.48 76.19 75.00 CPH-I 0.799(0.701~0.896) 86.54 96.83 78.95 63.16 交界性组与良性组 CA125 0.803(0.707~0.898) 76.19 76.19 51.61 85.71 HE4 0.826(0.720~0.932) 95.24 93.65 76.47 84.29 ROMA 0.821(0.706~0.935) 90.48 90.48 71.43 86.36 CPH-I 0.833(0.737~0.929) 96.83 96.83 80.00 83.33 表 4 不同绝经状态下4种指标的诊断效能
组别 绝经状态 指标 AUC(95% CI) 灵敏度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) 早期恶性组与良性组 绝经前 CA125 0.785(0.664~0.906) 95.24 71.79 59.26 84.85 HE4 0.900(0.804~0.996) 71.43 92.31 83.33 85.71 ROMA 0.905(0.804~0.999) 85.71 87.18 78.26 91.89 CPH-I 0.935(0.875~0.996) 71.43 94.87 88.24 86.05 绝经后 CA125 0.958(0.910~1.000) 96.77 83.33 88.24 95.24 HE4 0.991(0.974~1.000) 90.32 95.83 96.55 88.46 ROMA 0.995(0.983~1.000) 96.77 95.83 96.77 95.83 CPH-I 0.992(0.976~1.000) 96.77 95.83 96.77 95.83 早期恶性组与交界性组 绝经前 CA125 0.627(0.445~0.809) 95.24 60.00 64.00 54.55 HE4 0.643(0.453~0.832) 71.43 53.33 65.22 53.85 ROMA 0.653(0.464~0.841) 85.71 60.00 66.67 66.67 CPH-I 0.701(0.521~0.882) 71.43 46.67 68.18 57.14 绝经后 CA125 0.878(0.773~0.983) 96.77 77.77 81.08 66.67 HE4 0.892(0.792~0.993) 90.32 55.55 84.85 57.14 ROMA 0.907(0.816~0.998) 96.77 66.67 83.33 75.00 CPH-I 0.914(0.826~1.000) 96.77 55.55 85.71 80.00 交界性组与良性组 绝经前 CA125 0.771(0.641~0.901) 60.00 71.79 45.00 82.35 HE4 0.817(0.679~0.955) 53.33 92.31 80.00 84.09 ROMA 0.826(0.693~0.959) 60.00 87.18 64.29 85.00 CPH-I 0.846(0.737~0.956) 46.67 94.87 87.50 82.61 绝经后 CA125 0.852(0.712~0.992) 77.77 83.33 63.64 90.91 HE4 0.921(0.829~1.000) 55.55 95.83 83.33 85.19 ROMA 0.944(0.867~1.000) 66.67 95.83 60.00 68.97 CPH-I 0.894(0.782~1.000) 55.55 95.83 83.33 85.19 -
[1] SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33. doi: 10.3322/caac.21654 [2] 陈姝, 张競, 李燕华. CD24和Siglec-10在上皮性卵巢癌组织中的表达及意义[J]. 中华全科医学, 2021, 19(3): 428-431. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY202103028.htm [3] LHEUREUX S, GOURLEY C, VERGOTE I, et al. Epithelial ovarian cancer[J]. Lancet, 2019, 393(10177): 1240-1253. doi: 10.1016/S0140-6736(18)32552-2 [4] NATOLI M, BONITO N, ROBINSON J D, et al. Human ovarian cancer in-trinsic mechanisms regulate lymphocyte activation in response to im-mune checkpoint blockade[J]. Cancer Immunol Immunother, 2020, 69(8): 1391-1401. doi: 10.1007/s00262-020-02544-5 [5] ASLAN K, ONAN M A, YILMAZ C, et al. Comparison of HE4, CA125, ROMA score and ultrasound score in the differential diagnosis of ovarian masses[J]. Gynecol Obstet Hum Reprod, 2020, 49(5): 101713. doi: 10.1016/j.jogoh.2020.101713 [6] DUMONT S, JAN Z, HEREMANS R, et al. Organoids of epithelial ovarian cancer as an emerging preclinical in vitro tool: A review[J]. J Ovarian Res, 2019, 12(1): 105. doi: 10.1186/s13048-019-0577-2 [7] CHARKHCHI P, CYBULSKI C, GRONWALD J, et al. CA125 and ovarian cancer: A comprehensive review[J]. Cancers(Basel), 2020, 12(12): 3730. [8] SCALETTA G, PLOTTI F, LUVERO D, et al. The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: A systematic review[J]. Expert Rev Anticancer Ther, 2017, 17(9): 827-839. doi: 10.1080/14737140.2017.1360138 [9] CHENG H Y, ZENG L, YE X, et al. Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: A prospective cross-sectional study in healthy Chinese people[J]. Chin Med J (Engl), 2020, 133(11): 1285-1291. doi: 10.1097/CM9.0000000000000785 [10] MOORE R G, MCMEEKIN D S, BROWN A K, et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass[J]. Gynecol Oncol, 2009, 112(1): 40-46. doi: 10.1016/j.ygyno.2008.08.031 [11] DOCHEZ V, CAILLON H, VAUCEL E, et al. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review[J]. J Ovarian Res, 2019, 12(1): 28. doi: 10.1186/s13048-019-0503-7 [12] KARLSEN M A, HOGDALL E V, CHRISTENSEN I J, et al. A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer-An international multicenter study in women with an ovarian mass[J]. Gynecol Oncol, 2015, 138(3): 640-646. doi: 10.1016/j.ygyno.2015.06.021 [13] HENDERSON J T, WEBBER E M, SAWAYA G F. Screening for ovarian cancer: Updated evidence report and systematic review for the US preventive services task force[J]. JAMA, 2018, 319(6): 595-606. doi: 10.1001/jama.2017.21421 [14] CHUDECKA-GLAZ A, CYMBALUK-PLOSKA A, WEZOWSKA M, et al. Could HE4 level measurements during first-line chemotherapy predict response to treatment among ovarian cancer patients?[J]. PLoS One, 2018, 13(3): e0194270. doi: 10.1371/journal.pone.0194270 [15] KIM B, PARK Y, KIM B, et al. Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer[J]. J Clin Lab Anal, 2019, 33(1): e22624. doi: 10.1002/jcla.22624 [16] CHOI H J, LEE Y Y, SOHN I, et al. Comparison of CA 125 alone and risk of ovarian malignancy algorithm (ROMA) in patients with adnexal mass: A multicenter study[J]. Curr Probl Cancer, 2020, 44(2): 100508. doi: 10.1016/j.currproblcancer.2019.100508 [17] GENTRY-MAHARAJ A, BLYUSS O, RYAN A, et al. Multi-marker longitudinal algorithms incorporating HE4 and CA125 in ovarian cancer screening of postmenopausal women[J]. Cancers(Basel), 2020, 12(7): 1931. http://www.researchgate.net/publication/343103659_Multi-Marker_Longitudinal_Algorithms_Incorporating_HE4_and_CA125_in_Ovarian_Cancer_Screening_of_Postmenopausal_Women [18] ZHANG L, CHEN Y, WANG K. Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis[J]. Curr Probl Cancer, 2019, 43(2): 135-144. doi: 10.1016/j.currproblcancer.2018.06.001 [19] YANG W L, LU Z, BAST R C J R. The role of biomarkers in the management of epithelial ovarian cancer[J]. Expert Rev Mol Diagn, 2017, 17(6): 577-591. doi: 10.1080/14737159.2017.1326820 [20] LYCKE M, KRISTJANSDOTTIR B, SUNDFELDT K. A multicenter clinical trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index[J]. Gynecol Oncol, 2018, 151(1): 159-165. doi: 10.1016/j.ygyno.2018.08.025 [21] 邢华蕊, 冯亚妮, 黎小芳, 等. 血清肿瘤标志物水平与卵巢癌患者病理特征及预后的关系分析[J]. 河北医学, 2020, 26(8): 1404-1408. doi: 10.3969/j.issn.1006-6233.2020.08.040 [22] DOCHEZ V, RANDET M, RENAUDEAU C, et al. Efficacy of HE4, CA125, risk of malignancy index and risk of ovarian malignancy index to detect ovarian cancer in women with presumed benign ovarian tumours: A prospective, multicentre trial[J]. J Clin Med, 2019, 8(11): 1784. doi: 10.3390/jcm8111784 [23] Amerivan College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Gynecology. Practice bulletin No. 174: Evaluation and management of adnexal masses[J]. Obstet Gynecol, 2016, 128(5): e210-e226. doi: 10.1097/AOG.0000000000001768 [24] YOSHIDA A, DERCHAIN S F, PITTA D R, et al. Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?[J]. Gynecol Oncol, 2016, 140(3): 481-485. doi: 10.1016/j.ygyno.2016.01.023 [25] 龚时鹏, 陈咏宁, 张雅迪, 等. 血清CA125和HE4水平及ROMA、CPH-I模型在鉴别卵巢良恶性肿瘤中的价值对比[J]. 南方医科大学学报, 2019, 39(12): 1393-1401. https://www.cnki.com.cn/Article/CJFDTOTAL-DYJD201912003.htm -