尿多胺作为卵巢癌的生物标志物

Urinary Polyamines as Biomarkers for Ovarian Cancer.

作者信息

Niemi Riikka Johanna, Roine Antti N, Häkkinen Merja R, Kumpulainen Pekka S, Keinänen Tuomo A, Vepsäläinen Jouko J, Lehtimäki Terho, Oksala Niku K, Mäenpää Johanna U

机构信息

*Department of Obstetrics and Gynecology, Tampere University Hospital; †Faculty of Medicine and Life Sciences, University of Tampere, Tampere; ‡School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio; §Digital Health Solutions; ∥Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences; ¶Department of Surgery, Faculty of Medicine and Life Sciences, University of Tampere; #Department of Vascular Surgery, Tampere University Hospital; and **Department of Obstetrics and Gynecology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

出版信息

Int J Gynecol Cancer. 2017 Sep;27(7):1360-1366. doi: 10.1097/IGC.0000000000001031.

DOI:10.1097/IGC.0000000000001031

PMID:28604456

Abstract

OBJECTIVES

Elevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography-tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women.

MATERIALS AND METHODS

In this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group.

RESULTS

Twenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N,N-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N,N-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I-II) versus benign tumors (P = 0.017). N,N-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%).

CONCLUSIONS

Urinary N,N-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.

摘要

目的

在包括卵巢癌在内的恶性肿瘤患者的尿液中发现多胺浓度升高。以往的研究存在检测方法标准化程度低的问题。我们的液相色谱 - 串联质谱法（LC-MS/MS）能够同时对大多数已知多胺进行标准化分析。液相色谱 - 串联质谱法此前尚未用于绝经后女性卵巢肿瘤的鉴别诊断。

材料与方法

在这项前瞻性研究中，招募了出现附件包块的绝经后女性（n = 71），并将计划接受手术的生殖器脱垂或尿失禁女性（n = 22）作为对照纳入研究。为分析多胺，在手术前采集晨尿样本。在研究组中测定术前血清CA125浓度。

结果

23例患有良性卵巢肿瘤和37例患有恶性卵巢肿瘤的女性符合条件。在所有分析的多胺中，除了对照组与良性肿瘤组外，只有尿中N，N - 二乙酰精胺在所有组之间显示出统计学上的显著差异。与良性肿瘤相比，恶性肿瘤中的N，N - 二乙酰精胺升高（P < 0.001）；与低恶性潜能肿瘤相比，高等级肿瘤中的N，N - 二乙酰精胺升高（P < 0.001）；与I至II期癌症相比，III至IV期癌症中的N，N - 二乙酰精胺升高（P < 0.001）；甚至在早期癌症（I - II期）与良性肿瘤相比时N，N - 二乙酰精胺也升高（P = 0.017）。与CA125（临界值为35 kU/L，敏感性为75.7%；特异性为69.6%）相比，N，N - 二乙酰精胺在区分良性和恶性卵巢肿瘤方面具有更高的敏感性（86.5%）但更低的特异性（65.2%）。