Takahashi Naoki, Yamada Yasuhide, Furuta Koh, Nagashima Kengo, Kubo Akiko, Sasaki Yusuke, Shoji Hirokazu, Honma Yoshitaka, Iwasa Satoru, Okita Natsuko, Takashima Atsuo, Kato Ken, Hamaguchi Tetsuya, Shimada Yasuhiro
Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Division of Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
Cancer Sci. 2015 May;106(5):604-10. doi: 10.1111/cas.12642. Epub 2015 Apr 29.
Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients.
皮肤毒性是一种已知的临床特征，用于预测转移性结直肠癌（mCRC）患者接受抗表皮生长因子受体（EGFR）抗体治疗的预后。在mCRC患者接受抗EGFR抗体治疗之前，尚无预测皮肤毒性的生物标志物。2008年8月至2011年8月期间，从接受抗EGFR抗体治疗的KRAS野生型（WT）患者中获取治疗前血清样本。通过酶联免疫吸附测定法（ELISA）测量配体的血清水平。共有103例KRAS WT患者纳入本研究。皮肤毒性为高级别（2 - 3级）的患者的无进展生存期和总生存期显著长于低级别（0 - 1级）皮肤毒性的患者（中位无进展生存期，6.4个月对2.4个月，P < 0.001；中位总生存期，14.6个月对7.1个月，P = 0.006）。低/高级别皮肤毒性组之间，表皮调节素（EREG）、双调蛋白（AREG）和肝细胞生长因子（HGF）的血清水平分布存在显著差异（分别为P < 0.048、P < 0.012、P < 0.012）。此外，根据 Cochr an - Armitage检验，HGF、EREG和AREG的血清水平与皮肤毒性级别呈负相关（分别为P = 0.019、P = 0.047、P = 0.021）。我们的研究表明，HGF、EREG和AREG等血清水平可能是预测皮肤毒性级别和抗EGFR抗体治疗预后的重要标志物，这有助于改善mCRC患者皮肤毒性的管理和生存时间。
