Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions: The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.
目的： 通过检测结直肠癌患者血浆与组织中KRAS、NRAS、BRAF及PIK3CA基因突变情况，分析血浆与组织基因突变检测结果的一致性，为血浆可替代组织进行基因突变检测提供依据。 方法： 收集2016年10月至2017年10月在吉林大学白求恩第一医院进行手术切除的结直肠癌及其相应的患者血浆标本175例，其中男性101例，女性74例；患者年龄28~85岁，中位年龄59岁。运用二代测序法分别对175例结直肠癌患者的血浆和对应肿瘤组织的KRAS、NRAS、BRAF及PIK3CA基因突变状态进行检测。 结果： 以组织样本检测结果为金标准，KRAS基因在血浆和组织检测一致率为81.1%（Kappa值=0.543），NRAS检测一致率为99.4%（Kappa值=0.886），BRAF检测一致率为99.4%（Kappa值=0.886），PIK3CA检测一致率为97.7%（Kappa值=0.714），结果一致性较好；血浆中基因突变检测阳性率与结直肠癌患者的分期有关（P=0.001），与性别（P=0.468）、年龄（P=1.000）均无关。 结论： 血浆检测KRAS、NRAS、BRAF、PIK3CA基因突变与组织的一致性较好。虽然肿瘤组织仍是最佳的检测标本，但在结直肠癌患者无法获得肿瘤组织标本时，尤其是晚期已发生转移的患者，可考虑用血浆代替组织检测KRAS、NRAS、BRAF及PIK3CA的突变状态，用于指导患者的靶向治疗。.
Keywords: Colorectal neoplasms; DNA mutational analysis; DNA, neoplasm; Genes, ras; Molecular targeted therapy.