Fang Wen-Liang, Lan Yuan-Tzu, Huang Kuo-Hung, Liu Chien-An, Hung Yi-Ping, Lin Chien-Hsing, Jhang Fang-Yu, Chang Shih-Ching, Chen Ming-Huang, Chao Yee, Lin Wen-Chang, Lo Su-Shun, Fen-Yau Li Anna, Wu Chew-Wun, Chiou Shih-Hwa, Shyr Yi-Ming
Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
Int J Cancer. 2016 Jun 15;138(12):2974-83. doi: 10.1002/ijc.30018. Epub 2016 Feb 18.
With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.
随着分子技术的进步，循环血浆DNA（cpDNA）的检测在临床上已切实可行。然而，cpDNA水平在胃癌中的作用尚未得到充分了解。本研究评估了原发性肿瘤中的突变谱，并阐明了277例晚期胃癌患者中cpDNA定量和定性改变的临床实用性。通过TaqMan定量聚合酶链反应测量cpDNA的浓度，并研究了8个基因中的68个突变以检测cpDNA突变。I期、II期和III期胃癌患者的cpDNA浓度中位数分别为3979、3390和4278拷贝/毫升，而IV期胃癌患者的cpDNA浓度中位数增加至11380拷贝/毫升（p<0.001）。在35例存在cpDNA突变的患者中，IV期患者（100%）比I期（33.3%）、II期（75%）和III期患者（66.7%）更有可能表现出高cpDNA水平（p=0.037）。与cpDNA水平低的患者相比，cpDNA水平高的患者更有可能发生腹膜复发，且5年总生存率显著更低（39.2%对45.8%，p=0.039）。仅对于晚期（III期或IV期）胃癌，存在cpDNA突变的患者更有可能发生血管侵犯（20%对2.4%，p=0.036），且其5年总生存率低于无cpDNA突变的患者（5.6%对31.5%，p=0.028）。高cpDNA水平与晚期胃癌患者的腹膜复发和不良预后相关；存在cpDNA突变与晚期胃癌患者的不良预后相关。
