转移性结直肠癌患者中HER2/neu、HER3和NRG1表达的患病率及其对预后的影响
Prevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancer.
作者信息
Stahler Arndt, Heinemann Volker, Neumann Jens, Crispin Alexander, Schalhorn Andreas, Stintzing Sebastian, Giessen-Jung Clemens, Fischer von Weikersthal Ludwig, Vehling-Kaiser Ursula, Stauch Martina, Quietzsch Detlef, Holch Julian W, Kruger Stephan, Haas Michael, Michl Marlies, von Einem Jobst, Kirchner Thomas, Jung Andreas, Modest Dominik P
机构信息
aDepartment of Medicine III, Comprehensive Cancer Centre, University Hospital Grosshadern bDepartment of Pathology cInstitute of Medical Informatics, Biometry, and Epidemiology, University of Munich dGerman Department of Translational Cancer Research (DKTK), German Cancer Research Centre (DKFZ), Heidelberg eKlinikum St Marien, Oncology, Amberg fOncological surgery, Landshut gCentre of ambulatory treatment for oncological and haematological diseases, Kronach hKlinikum Chemnitz, Chemnitz, Germany.
出版信息
Anticancer Drugs. 2017 Aug;28(7):717-722. doi: 10.1097/CAD.0000000000000510.
Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients. High versus low NRG1 expression significantly affected progression-free survival (PFS) [4.7 vs. 8.2 months, hazard ratio (HR): 2.45; 95% confidence interval (CI): 1.45-4.13; P=0.001], but not overall survival (OS) (15.5 vs. 20.7 months, HR: 1.33; 95% CI: 0.76-2.35; P=0.32). High versus low HER3 expression (PFS: 7.1 vs. 8.8 months, HR: 1.11; 95% CI: 0.82-1.50; P=0.50; OS: 19.8 vs. 21.1 months, HR: 0.95; 95% CI: 0.70-1.30; P=0.75) and high compared with low HER2/neu expression (PFS: 7.7 vs. 8.0 months, HR: 1.07; 95% CI: 0.71-1.60; P=0.75; OS: 16.6 vs. 21.1 months, HR: 1.13; 95% CI: 0.75-1.71; P=0.57) did not influence outcome. High NRG1 expression was associated with inferior PFS in the FIRE-1 trial. We did not detect a prognostic impact of HER2/neu and HER3 overexpression in mCRC. The frequency of overexpression was comparable with other studies.
我们的目的是探讨HER2/neu、HER3受体及其配体神经调节蛋白（NRG1）的表达对转移性结直肠癌（mCRC）患者预后的影响。在208例接受5-氟尿嘧啶/亚叶酸钙联合伊立替康或伊立替康联合奥沙利铂作为一线治疗的mCRC患者中评估了NRG1、HER2/neu和HER3的表达。生物标志物表达与患者预后相关。在208例患者中评估了NRG1（低表达：192例 vs. 高表达：16例）、HER2/neu（低表达：201例 vs. 高表达：7例）和HER3（低表达：69例 vs. 高表达：139例）的表达。NRG1高表达与低表达相比显著影响无进展生存期（PFS）[4.7个月 vs. 8.2个月，风险比（HR）：2.45；95%置信区间（CI）：1.45 - 4.13；P = 0.001]，但对总生存期（OS）无影响（15.5个月 vs. 20.7个月，HR：1.33；95% CI：0.76 - 2.35；P = 0.32）。HER3高表达与低表达相比（PFS：7.1个月 vs. 8.8个月，HR：1.11；95% CI：0.82 - 1.50；P = 0.50；OS：19.8个月 vs. 21.1个月，HR：0.95；95% CI：0.70 - 1.30；P = 0.75）以及HER2/neu高表达与低表达相比（PFS：7.7个月 vs. 8.0个月，HR：1.07；95% CI：0.71 - 1.60；P = 0.75；OS：16.6个月 vs. 21.1个月，HR：1.13；95% CI：0.75 - 1.71；P = 0.57）均不影响预后。在FIRE - 1试验中，NRG1高表达与较差的PFS相关。我们未检测到HER2/neu和HER3过表达对mCRC的预后影响。过表达频率与其他研究相当。
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