Luangdilok Sutima, Wanchaijiraboon Passakorn, Chantranuwatana Poonchavist, Teerapakpinyo Chinachote, Shuangshoti Shanop, Sriuranpong Virote
Department of Biochemistry, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Division of Medical Oncology, Department of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Transl Lung Cancer Res. 2019 Dec;8(6):959-966. doi: 10.21037/tlcr.2019.12.01.
East Asian, including Thailand, lung cancer population may have a relatively lower prevalence of mutations than Caucasians. We investigated the prevalence and clinical characteristics of -driven non-small cell lung cancer (NSCLC) patients and the expression of cyclin D1, one of the KRAS downstream targets.
Lung cancer patients who received treatment at the King Chulalongkorn Memorial Hospital between January 2015 and July 2017 were enrolled. We identified mutations using allele specific PCR mutation testing. Cyclin D1 expression was determined using immunohistochemistry.
After excluding 376 mutations and inadequate samples, we enrolled 95 patients eligible for mutation testing. mutations were identified in 28 out of 95 patients. There were 26 patients with codon 12/13 and 2 patients with codon 61 mutations. The prevalence of mutations among informative samples was 28 out of 357 (7.8%) which was relatively lower than that reported in Caucasian population. Smoking and male were significantly associated with mutations. The prognosis of -mutant NSCLC patients in particular codon 61 mutations was worse than that found in and wild-type ( WT/ WT) NSCLC patients (P0.048). The levels of cyclin D1 expression in -mutant NSCLC were significantly higher than those in WT/ WT NSCLC (P0.02). A better prognosis of mutant NSCLC patients with low cyclin D1 expression was observed when compared with those with high cyclin D1 expression (median overall survival 41.7 . 3.5 months, P0.037).
We found a moderate prevalence of mutations in lung cancer in Thailand. Clinical characteristics were similar to those of Caucasian population. Most mutant NSCLC had high cyclin D1 expression. Cyclin D1 expression may serve as a useful prognostic biomarker in -mutant lung cancer. Validation of this finding in larger cohort is required.
包括泰国在内的东亚肺癌人群中，KRAS基因突变的患病率可能相对低于白种人。我们调查了KRAS驱动的非小细胞肺癌（NSCLC）患者的患病率和临床特征，以及KRAS下游靶点之一细胞周期蛋白D1的表达情况。
纳入2015年1月至2017年7月在朱拉隆功国王纪念医院接受治疗的肺癌患者。我们使用等位基因特异性PCR突变检测来鉴定KRAS基因突变。采用免疫组织化学法测定细胞周期蛋白D1的表达。
排除376例KRAS基因突变和样本不足的病例后，我们纳入了95例符合KRAS基因突变检测条件的患者。95例患者中有28例检测到KRAS基因突变。其中26例为KRAS密码子12/13突变，2例为KRAS密码子61突变。在有信息的样本中，KRAS基因突变的患病率为357例中的28例（7.8%），相对低于白种人群的报道。吸烟和男性与KRAS基因突变显著相关。KRAS突变的NSCLC患者，尤其是密码子61突变患者的预后比KRAS野生型（WT/WT）NSCLC患者更差（P<0.048）。KRAS突变的NSCLC中细胞周期蛋白D1的表达水平显著高于KRAS WT/WT NSCLC（P<0.02）。与细胞周期蛋白D1高表达的KRAS突变NSCLC患者相比，细胞周期蛋白D1低表达的患者预后更好（中位总生存期41.7对3.5个月，P<0.037）。
我们发现泰国肺癌患者中KRAS基因突变的患病率适中。临床特征与白种人群相似。大多数KRAS突变的NSCLC细胞周期蛋白D1表达较高。细胞周期蛋白D1表达可能是KRAS突变肺癌的一个有用的预后生物标志物。需要在更大的队列中验证这一发现。
