Kim Seung Tae, Ahn Tae Jin, Lee Eunjin, Do In-Gu, Lee Su Jin, Park Se Hoon, Park Joon Oh, Park Young Suk, Lim Ho Yeong, Kang Won Ki, Kim Suk Hyeong, Lee Jeeyun, Kim Hee Cheol
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
BMC Cancer. 2015 Oct 20;15:747. doi: 10.1186/s12885-015-1759-y.
More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC.
We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes.
BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS.
The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC.
在转移性结直肠癌（mCRC）中，超过半数基于KRAS突变状态选择的患者对西妥昔单抗治疗无反应。我们设计了一项研究，以确定可作为mCRC中西妥昔单抗治疗指标的其他生物标志物。
我们研究了58例接受西妥昔单抗联合伊立替康（CI）治疗的野生型KRAS结直肠癌患者的肿瘤样本。我们对BRAF或PIK3CA的突变进行了基因分型，并全面分析了522个激酶基因的表达情况。
5.1%（3/58）的患者检测到BRAF突变。所有50例患者均显示PIK3CA野生型。通过监督分类分析比较了将有或无疾病控制至CI的患者分类的基因表达模式。PSKH1、TLK2和PHKG2在疾病控制至IC的患者中显著过表达。PSKH1（r = 0.462，p < 0.001）和TLK2（r = 0.361，p = 0.005）的较高表达值与延长的无进展生存期显著相关。
这项工作的结果表明，PSKH1、TLK2和PHKG2等激酶基因的表达性质可能有助于预测CI在野生型KRAS结直肠癌中的疗效。BRAF或PIK3CA的突变在野生型KRAS结直肠癌中是罕见的亚组。
