Thymidylate synthase mRNA levels in plasma and tumor as potential predictive biomarkers for raltitrexed sensitivity in gastric cancer
Thymidylate synthase mRNA levels in plasma and tumor as potential predictive biomarkers for raltitrexed sensitivity in gastric cancer
复制标题
血浆和肿瘤中胸苷酸合酶 mRNA 水平作为胃癌雷替曲塞敏感性的潜在预测生物标志物
DOI：
10.1002/ijc.27530
复制
发表时间：
2012-09-15
影响因子：
6.4
通讯作者：
Guan, Wenxian
中科院分区：
文献类型：
--
作者：
Shen, Jie;Wang, Hao;Guan, Wenxian
目前可用的不同化疗剂仅在某些患者亚群中有效。预测性生物标志物将有助于选择这些药物，并可以通过更个性化的化疗方法提高临床效率。雷替曲塞是一种新型水溶性喹唑啉叶酸类似物，可提高胃癌治疗的效率，但其预测生物标志物仍不清楚。本研究的目的是探讨血浆和肿瘤胸苷酸合成酶（TS）mRNA水平作为雷替曲塞在胃癌中的预测生物标志物的作用。总共收集了125例新鲜切除的胃肿瘤标本和相应的手术前血液样本。通过组织培养药物反应试验程序测定雷替曲塞敏感性。采用定量逆转录聚合酶链反应（RT-PCR）检测肿瘤组织和血浆中TS mRNA水平。恶性肿瘤患者血浆TS mRNA水平显著高于正常对照组（p = 0.009），并与肿瘤组织TS mRNA水平显著相关（r = 0.665，p < 0.001）。雷替曲塞敏感组的肿瘤和血浆TS mRNA表达水平显著低于耐药组（分别为p = 0.007和0.013）。基于血浆TS mRNA水平的雷替曲塞敏感性预测的敏感性和准确性分别为82%和60%，而基于肿瘤TS mRNA的预测达到70%的敏感性和68%的准确性。结果表明，血浆TS mRNA水平可反映肿瘤TS mRNA水平，两者均可用于预测胃癌患者雷替曲塞敏感性。
Different chemotherapeutic agents currently available are effective only in certain subsets of patients. Predictive biomarkers will be helpful in choosing those agents and can improve the clinical efficiency by a more personalized chemotherapeutic approach. Raltitrexed is a novel water‐soluble quinazoline folate analogue and can improve the efficiency of gastric cancer treatment, but its predictive biomarker remains unclear. The aim of our study was to investigate the role of plasma and tumor thymidylate synthase (TS) mRNA levels as predictive biomarkers for raltitrexed in gastric cancer. In total, 125 freshly removed gastric tumor specimens and corresponding blood samples before surgery were collected. Raltitrexed sensitivity was determined by histoculture drug response assay procedures. TS mRNA levels in tumor and plasma were determined by quantitative reverse transcription polymerase chain reaction. Plasma TS mRNA level in cancer patients was significantly higher than in healthy subjects (p = 0.009) and was significantly correlated with TS mRNA level in tumor tissues (r = 0.665, p < 0.001). Tumor and plasma TS mRNA expression levels were significantly lower in raltitrexed‐sensitive group than in resistant group (p = 0.007 and 0.013, respectively). The sensitivity and accuracy of raltitrexed sensitivity prediction based on plasma TS mRNA levels were 82 and 60%, respectively, whereas the prediction based on tumor TS mRNA reached 70% sensitivity and 68% accuracy. These results indicate that TS mRNA level in plasma can mirror tumor TS mRNA level, and both of them can be used to predict raltitrexed sensitivity in gastric cancer.