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血清淀粉样蛋白 A:子宫内膜癌的新型生物标志物。

Serum amyloid A: a novel biomarker for endometrial cancer.

机构信息

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.

出版信息

Cancer. 2010 Feb 15;116(4):843-51. doi: 10.1002/cncr.24838.

Abstract

BACKGROUND

The authors investigated the expression of serum amyloid A (SAA) in endometrial endometrioid carcinoma and evaluated its potential as a serum biomarker.

METHODS

SAA gene and protein expression levels were evaluated in endometrial endometrioid carcinoma and normal endometrial tissues, by real-time polymerase chain reaction (PCR), immunohistochemistry (IHC), and flow cytometry. SAA concentration in 194 serum samples from 50 healthy women, 42 women with benign diseases, and 102 patients including 49 grade 1, 38 grade 2, and 15 grade 3 endometrial endometrioid carcinoma was also studied by a sensitive bead-based immunoassay.

RESULTS

SAA gene expression levels were significantly higher in endometrial endometrioid carcinoma when compared with normal endometrial tissues (mean copy number by real-time PCR = 182 vs 1.9; P = .001). IHC revealed diffuse cytoplasmic SAA protein staining in poorly differentiated endometrial endometrioid carcinoma tissues. High intracellular levels of SAA were identified in primary endometrial endometrioid carcinoma cell lines evaluated by flow cytometry, and SAA was found to be actively secreted in vitro. SAA concentrations (microg/mL) had medians of 6.0 in normal healthy women and 6.0 in patients with benign disease (P = .92). In contrast, SAA values in the serum of endometrial endometrioid carcinoma patients had a median of 23.7, significantly higher than those of the healthy group (P = .001) and benign group (P = .001). Patients harboring G3 endometrial endometrioid carcinoma were found to have SAA concentrations significantly higher than those of G1/G2 patients.

CONCLUSIONS

SAA is not only a liver-secreted protein, but is also an endometrial endometrioid carcinoma cell product. SAA is expressed and actively secreted by G3 endometrial endometrioid carcinoma, and it is present in high concentration in the serum of endometrial endometrioid carcinoma patients. SAA may represent a novel biomarker for endometrial endometrioid carcinoma to monitor disease recurrence and response to therapy.

摘要

背景

作者研究了血清淀粉样蛋白 A(SAA)在子宫内膜样腺癌中的表达,并评估了其作为血清生物标志物的潜力。

方法

通过实时聚合酶链反应(PCR)、免疫组织化学(IHC)和流式细胞术评估子宫内膜样腺癌和正常子宫内膜组织中的 SAA 基因和蛋白表达水平。通过敏感的基于珠的免疫测定法研究了来自 50 名健康女性、42 名良性疾病女性和 102 名患者(包括 49 名 1 级、38 名 2 级和 15 名 3 级子宫内膜样腺癌)的 194 份血清样本中的 SAA 浓度。

结果

与正常子宫内膜组织相比,子宫内膜样腺癌中 SAA 基因表达水平显著升高(实时 PCR 平均拷贝数=182 比 1.9;P=.001)。免疫组织化学显示,低分化子宫内膜样腺癌组织中存在弥漫性细胞质 SAA 蛋白染色。通过流式细胞术鉴定,在原发性子宫内膜样腺癌细胞系中检测到高细胞内 SAA 水平,并且体外发现 SAA 被主动分泌。正常健康女性和良性疾病患者的血清 SAA 浓度(μg/mL)中位数分别为 6.0,差异无统计学意义(P=.92)。相比之下,子宫内膜样腺癌患者的 SAA 值中位数为 23.7,明显高于健康组(P=.001)和良性组(P=.001)。研究发现,患有 G3 子宫内膜样腺癌的患者的 SAA 浓度明显高于 G1/G2 患者。

结论

SAA 不仅是一种肝脏分泌的蛋白质,也是子宫内膜样腺癌细胞的产物。G3 子宫内膜样腺癌表达并主动分泌 SAA,且在子宫内膜样腺癌患者的血清中含量较高。SAA 可能代表一种新的子宫内膜样腺癌生物标志物,可用于监测疾病复发和治疗反应。

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