Liu Yanzhuo, Yang Maozhu, Jiang Tao, Lan Chunbin, Yuan Hao, Li Guiquan, Jia Guiqing, Wang Kang, Zhao Gaoping
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610000, China.
Institute of Chengdu Biology and Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu 610000, China.
Gastroenterol Res Pract. 2019 Jan 31;2019:1750329. doi: 10.1155/2019/1750329. eCollection 2019.
Circulating tumor DNA (ctDNA) derived from tumors is a promising biomarker for monitoring tumor status and evaluating therapeutic effects and prognosis. We studied the plasma human epidermal growth factor receptor 2 (HER2) amplification in gastric cancer (GC) patients by droplet digital PCR (ddPCR) during therapy with trastuzumab.
A total of 12 patients were recruited after surgery. All patients received FOLFOX chemotherapy combined with trastuzumab as a treatment regimen. During the 12 months of the follow-up period, using elongation factor Tu GTP binding domain containing 2 (EFTUD2) as a reference gene, plasma HER2 to EFTUD2 ratios (the HER2 ratio) were determined for each patient every 2 months by ddPCR.
The concordance rate of HER2 amplification examined in plasma and formalin-fixed paraffin-embedded (FFPE) samples with ddPCR was 81.4%, with a sensitivity of 76.5% and a specificity of 83.8%. Plasma HER2 ratios were correlated with the primary tumor size ( < 0.01). A significant decrease in the plasma HER2 ratio was found after two months of treatment ( < 0.0001). Nine patients experienced partial response, and three patients had stable disease. Seven patients had progressive disease (PD) during follow-up, and four of them had died. The median progression-free survival (PFS) was 9.8 months. For each patient who developed PD, the plasma HER2 ratio was approximately 2.3-4.1 times higher than the cut-off value at the time of PD, which was the highest during the whole follow-up period.
Longitudinal monitoring for the plasma HER2 ratio by ddPCR in the clinical courses of GC patients holds great promise for use as an indicator of tumor progression and treatment efficacy.
源自肿瘤的循环肿瘤DNA（ctDNA）是监测肿瘤状态、评估治疗效果和预后的一种很有前景的生物标志物。我们通过液滴数字PCR（ddPCR）研究了胃癌（GC）患者在曲妥珠单抗治疗期间血浆中人表皮生长因子受体2（HER2）的扩增情况。
术后共招募了12例患者。所有患者接受FOLFOX化疗联合曲妥珠单抗作为治疗方案。在12个月的随访期内，以含伸长因子Tu GTP结合结构域2（EFTUD2）作为参照基因，每2个月通过ddPCR测定每位患者血浆中HER2与EFTUD2的比值（HER2比值）。
ddPCR检测血浆和福尔马林固定石蜡包埋（FFPE）样本中HER2扩增的符合率为81.4%，灵敏度为76.5%，特异性为83.8%。血浆HER2比值与原发肿瘤大小相关（<0.01）。治疗2个月后血浆HER2比值显著下降（<0.0001）。9例患者出现部分缓解，3例患者病情稳定。7例患者在随访期间病情进展（PD），其中4例死亡。中位无进展生存期（PFS）为9.8个月。对于每例出现PD的患者，血浆HER2比值比PD时的临界值高约2.3 - 4.1倍，这是整个随访期间的最高值。
在GC患者的临床病程中通过ddPCR对血浆HER2比值进行纵向监测，有望作为肿瘤进展和治疗疗效的指标。
