TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.
TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.
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发表时间：
2010-10
影响因子：
2
通讯作者：
H. Uramoto;T. Onitsuka;H. Shimokawa;T. Hanagiri
中科院分区：
文献类型：
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作者：
H. Uramoto;T. Onitsuka;H. Shimokawa;T. Hanagiri
背景培美曲塞（pemetrexed，PEM）是新一代抗叶酸剂，近年来被用于治疗晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）和恶性胸膜间皮瘤（malignant pleural mesothelioma，MPM）的非鳞状细胞癌（non-squamous cell carcinoma，SQ）。然而，目前还不存在用于选择适当候选人的有用标记。材料与方法肿瘤标本取自5例肺非SQ患者和8例接受手术并接受PEM的MPM患者。采用实时荧光定量PCR和免疫组化（IHC）方法检测原发肿瘤组织中胸苷酸合成酶（TS）/二氢叶酸还原酶（DHFR）和甘氨酰胺核糖核苷酸甲酰转移酶（GARFT）的mRNA和蛋白表达，并比较其表达状况和临床预后。结果非SQ型NSCLC患者TS、DHFR和GARFT mRNA水平的中位数分别为2.39、1.70和1.40。非SQ NSCLC患者的TS和DHFR蛋白水平平均总分分别为2和4。MPM患者TS、DHFR和GARFT mRNA水平的中位数分别为5.55、3.73和3.52。TS和DHFR蛋白水平在MPM患者中的平均总表达评分为1和3。TS/DPD/GARFT mRNA表达水平与PEM治疗的非SQ NSCLC和MPM患者的临床反应之间无显著相关性。结论TS、DHFR和GARFT mRNA和蛋白表达可能不是预测日本非SQ NSCLC和MPM患者临床反应的有用指标。为了开发生物标志物以确定PEM治疗的临床益处，有必要进行进一步的研究。
BACKGROUND Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. MATERIALS AND METHODS Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. RESULTS TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non-SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. CONCLUSION TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment.