早期乳腺癌患者的血清胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白-3（IGFBP-3）水平及循环肿瘤细胞（CTC）

Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

作者信息

Papadakis Georgios Z, Mavroudis Dimitrios, Georgoulias Vasilios, Souglakos John, Alegakis Athanasios K, Samonis George, Bagci Ulas, Makrigiannakis Antonis, Zoras Odysseas

机构信息

Faculty of Medicine, University of Crete, Greece; Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center (CC), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Department of Medical Oncology, University General Hospital of Heraklion, School of Medicine, University of Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.

出版信息

Growth Horm IGF Res. 2017 Apr;33:28-34. doi: 10.1016/j.ghir.2017.02.001. Epub 2017 Feb 16.

DOI:10.1016/j.ghir.2017.02.001

PMID:28258988

Abstract

OBJECTIVE

Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy.

DESIGN

171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS).

RESULTS

Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels.

CONCLUSIONS

IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer.

摘要

目的

胰岛素样生长因子（IGF）轴参与包括乳腺癌在内的多种实体瘤的人类肿瘤发生和转移发展。本研究的目的是评估在接受辅助化疗前后，IGF-1、IGF结合蛋白-3（IGFBP-3）血清水平与早期乳腺癌（EBC）女性外周血中循环肿瘤细胞（CTC）存在之间的关联。

设计

对171例早期乳腺腺癌患者进行回顾性评估。采用免疫放射分析（IRMA）法在手术治疗后和辅助化疗开始前采集的血样中体外测定IGF-1和IGFBP-3血清水平。通过使用定量实时逆转录聚合酶链反应（RT-PCR）检测细胞角蛋白-19（CK-19）mRNA转录本来评估CTC的存在。IGF-1、IGFBP-3血清水平与辅助化疗前后CTC的存在以及肿瘤特征（包括肿瘤大小、腋窝淋巴结状态、雌激素（ER）/孕激素（PR）和人表皮生长因子受体2（HER2）受体状态）相关。应用对数秩检验来研究IGF-1、IGFBP-3血清水平与无病生存期（DFI）和总生存期（OS）之间可能的关联。

结果

在辅助治疗开始前，IGF-1、IGFBP-3血清水平之间存在中度关联（Spearman秩相关系数=0.361，p<0.001），而在各年龄组之间存在显著差异（所有p值<0.05）。IGF-1血清水平与辅助化疗开始前（p=0.558）或完成后（p=0.474）CTC的存在无关。同样，IGFBP-3血清水平在辅助化疗完成前（p=0.487）或完成后（p=0.134）与可检测到的CTC均无显著关联。就DFI、OS而言，患者的临床结局与IGF-1（DFI：p=0.499；OS：p=0.220）或IGFBP-3（DFI：p=0.900；OS：p=0.406）血清水平之间无统计学显著关联。