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KMID : 0311120190600020132
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Yonsei Medical Journal
2019 Volume.60 No. 2 p.132 ~ p.139
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Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial
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Roh Chul-Kyu
Choi Yoon-Young
Choi Seo-Hee
Seo Won-Jun
Cho Min-Ah
Jang Eun-Ji
Son Tae-Il
Kim Hyoung-Il
Kim Hye-Seon
Hyung Woo-Jin
Huh Yong-Min
Noh Sung-Hoon
Cheong Jae-Ho
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Abstract
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Purpose: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
Materials and Methods: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status.
Results: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101?3.205), 2.399 (1.415?4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161?0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer.
Conclusion: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
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KEYWORD
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Gastric cancer, microsatellite instability, single patient classifier, EBV
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