EGFR、Her2 的表达可预测结直肠癌中与淋巴结转移（LNM）相关的转移。

Expression of EGFR, Her2 predict lymph node metastasis (LNM)-associated metastasis in colorectal cancer.

机构信息

Fudan University Shanghai Cancer Center, Department of Colorectal Cancer and Oncology, Shanghai Medical College Fudan University, Shanghai, China.

出版信息

Cancer Biomark. 2012;11(5):219-26. doi: 10.3233/CBM-2012-00282.

DOI:10.3233/CBM-2012-00282

PMID:23220854

Abstract

BACKGROUND

As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) have become efficacious drug targets in this setting. But until now, although above studies suggested that EGFR and Her2 may serve as effective biomarkers for targeted therapy in cancer patients with primary tumor, the information on these biomarkers in colorectal cancer is still limited in metastases.

OBJECTIVE

The purpose of this study is to evaluate the expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) on the lymph node metastasis (LNM) of colorectal cancer (CRC), develop LNM-associated biomarkers for CRC.

METHODS

Differences in EGFR and Her2 expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in a total of 126 Chinese colorectal carcinoma samples using quantitative real-time PCR analysis and western blot. Confirmation assay with immunohistochemistry (IHC) study was applied in the same samples. The relationship to clinicopathological parameters and prognosis of candidate biomarkers was also examined in the same samples.

RESULTS

EGFR and Her2 were significantly upregulated in LNM CRC compared to non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction, western blot. Similar results were confirmed in the immunohistochemistry (IHC) assay. Overexpression of EGFR and Her2 were significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that EGFR and Her2 expression were useful independent prognostic factor for recurrence and survival of CRC patients (P < 0.05).

CONCLUSIONS

EGFR and Her2 might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of EGFR or Her2 is a potential predict factor to the poor outcome in clinical colorectal cancer.

摘要

背景

表皮生长因子受体（EGFR）和人表皮生长因子受体 2（Her2）作为胃肠道癌症进展和化疗耐药的关键分子，已成为该领域有效的药物靶点。但到目前为止，尽管上述研究表明 EGFR 和 Her2 可能作为原发性肿瘤癌症患者靶向治疗的有效生物标志物，但在结直肠癌转移中，这些生物标志物的信息仍然有限。

目的

本研究旨在评估 EGFR 和 Her2 在结直肠癌（CRC）淋巴结转移（LNM）中的表达，为 CRC 开发与 LNM 相关的生物标志物。

方法

采用实时定量 PCR 分析和 Western blot 检测 126 例中国结直肠癌样本中 LNMCRC 和非 LNMCRC 中 EGFR 和 Her2 的表达差异。采用免疫组织化学（IHC）研究对同一样本进行验证检测。还在同一样本中检查了候选生物标志物与临床病理参数和预后的关系。

结果

实时定量聚合酶链反应、Western blot 证实 EGFR 和 Her2 在 LNMCRC 中明显上调。免疫组织化学（IHC）检测也证实了这一结果。EGFR 和 Her2 的过表达与 LNM（P < 0.001）、晚期 TNM 分期（P < 0.001）、5 年复发率增加（P < 0.001）和 5 年总生存率降低（P < 0.001）显著相关。单因素和多因素分析表明，EGFR 和 Her2 表达是 CRC 患者复发和生存的有用独立预后因素（P < 0.05）。