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间皮素和骨桥蛋白作为弥漫性恶性腹膜间皮瘤的循环标志物:一项初步研究。

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study.

机构信息

Peritoneal Malignancy Program, National Cancer Institute, via Venezian, 1, 20133, Milan, Italy.

Peritoneal Malignancy Program, National Cancer Institute, via Venezian, 1, 20133, Milan, Italy.

出版信息

Eur J Surg Oncol. 2018 Jun;44(6):792-798. doi: 10.1016/j.ejso.2018.02.010. Epub 2018 Feb 17.

Abstract

BACKGROUND

The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.

METHODS

Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC).

RESULTS

Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004).

CONCLUSION

When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.

摘要

背景

弥漫性恶性腹膜间皮瘤(DMPM)与其他腹膜表面恶性肿瘤(PSM)的鉴别诊断仍然具有挑战性。血清间皮素和骨桥蛋白越来越多地被用作胸膜间皮瘤的标志物,但它们在 DMPM 中的作用尚不清楚。我们评估了间皮素、骨桥蛋白、CEA、CA19.9、CA125 和 CA15.3 在 DMPM 患者中的诊断和预后价值。

方法

通过酶联免疫吸附试验(ELISA)在 30 名 DMPM 患者和 14 名其他 PSM 对照组患者的细胞减灭术和腹腔热灌注化疗(HIPEC)前测定标志物。绘制受试者工作特征(ROC)曲线。通过 ROC 曲线下面积(AUC-ROC)评估每个标志物的性能。

结果

DMPM 组的平均间皮素水平为 7.84ng/dl(SD=5.14),对照组为 3.00ng/dl(SD=1.25)(P=0.001)。两组的平均 CEA 水平分别为 5.3ng/dl(SD=4.7)和 61.96ng/dl(SD=112.5)(P=0.008)。骨桥蛋白(P=0.738)、CA19.9(P=0.081)、CA125(P=0.600)和 CA15.3(P=0.365)无统计学差异。CA19.9 的 AUC-ROC 为 0.836,间皮素为 0.812,CEA 为 0.793,CA125 为 0.652,骨桥蛋白为 0.531,CA15.3 为 0.481。使用 ROC 方法学选择的诊断截断值,间皮素>5.21ng/dl 的灵敏度、特异性、阳性和阴性预测值分别为 70.0%、100.0%、100.0%和 60.9%,CA19.9<8.8U/dl 的灵敏度、特异性、阳性和阴性预测值分别为 90.0%、85.7%、93.1%和 80.0%。多变量分析显示,骨桥蛋白与生存相关(危险率 6.46;95%CI 1.81-23.05;P=0.004)。

结论

在评估来源不明的 PSM 时,升高的间皮素伴低 CA19.9 可能增加 DMPM 的怀疑指数。骨桥蛋白作为 DMPM 的预后标志物值得进一步研究。

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