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人组织激肽释放酶7,一种使用新型蛋白质表达原位定量方法检测晚期卵巢癌的新型生物标志物。

Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression.

作者信息

Psyrri A, Kountourakis P, Scorilas A, Markakis S, Camp R, Diamandis E P, Dimopoulos M A, Kowalski D

机构信息

Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.

Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.

出版信息

Ann Oncol. 2008 Jul;19(7):1271-1277. doi: 10.1093/annonc/mdn035. Epub 2008 Mar 5.

DOI:10.1093/annonc/mdn035
PMID:18325919
Abstract

BACKGROUND

Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 7 (hk7) in ovarian cancer using a novel method of compartmentalized in situ protein analysis.

PATIENTS AND METHODS

A tissue array composed of 150 advanced-stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of kallikrein 7 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA).

RESULTS

Mean follow-up time of the cohort was 34.35 months. One hundred and twenty eight of 150 cases had sufficient tissue for AQUA. In univariate survival analysis, low tumor hk7 expression was associated with better outcome for overall survival (OS) and disease-free survival in 3 years (P values 0.032 and 0.037, respectively). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor hk7 expression level was the most significant predictor variable for OS (95% confidence interval 0.125-0.729, P = 0.007).

CONCLUSIONS

High tumor hk7 protein expression is associated with inferior patient outcome in ovarian cancer. hk7 may represent a promising prognostic factor in ovarian cancer.

摘要

背景

激肽释放酶是丝氨酸蛋白酶家族的一个亚群,被认为是癌症中重要的预后生物标志物。在此,我们试图使用一种新型的分区原位蛋白质分析方法来确定激肽释放酶7(hk7)在卵巢癌中的预后价值。

患者和方法

构建了一个由150例晚期卵巢癌组成的组织芯片,这些患者均接受了手术减瘤,随后进行铂类-紫杉醇(泰素)联合化疗。为了评估激肽释放酶7蛋白的表达,我们使用了基于免疫荧光的蛋白质分析自动原位定量测量方法(AQUA)。

结果

该队列的平均随访时间为34.35个月。150例病例中有128例有足够的组织用于AQUA分析。在单因素生存分析中,肿瘤hk7低表达与总生存期(OS)和3年无病生存期的较好预后相关(P值分别为0.032和0.037)。在多因素生存分析中,在调整了充分表征的预后变量后,肿瘤hk7低表达水平是OS的最显著预测变量(95%置信区间0.125 - 0.729,P = 0.007)。

结论

肿瘤hk7蛋白高表达与卵巢癌患者较差的预后相关。hk7可能是卵巢癌一个有前景的预后因素。

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