Quantitative Analysis of HER2 Amplification by Droplet Digital PCR in the Follow-Up of Gastric Cancer Patients Being Treated with Trastuzumab after Surgery. (31st January 2019)

• Record Type: Journal Article
• Authors: Liu, Yanzhuo; Yang, Maozhu; Jiang, Tao; Lan, Chunbin; Yuan, Hao; Li, Guiquan; Jia, Guiqing; Wang, Kang; Zhao, Gaoping
• Other Names: Marano Luigi Academic Editor.
• Is Part Of: Gastroenterology research and practice. Volume 2019(2019)
• Publication Date: 2019-01-31
• Subjects: Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; 616.33005
• DOI: 10.1155/2019/1750329
• Languages: English
• ISSNs: 1687-6121

Abstract

Abstract : Background . 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. Methods . 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. Results . 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 (p < 0.01 ). A significant decrease in the plasma HER2 ratio was found after two months of treatment (p < 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. Conclusion . 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.