TY - JOUR
T1 - Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer
T2 - Results from CLASSIC trial
AU - Roh, Chul Kyu
AU - Choi, Yoon Young
AU - Choi, Seohee
AU - Seo, Won Jun
AU - Cho, Minah
AU - Jang, Eunji
AU - Son, Taeil
AU - Kim, Hyoung Il
AU - Kim, Hyeseon
AU - Hyung, Woo Jin
AU - Huh, Yong Min
AU - Noh, Sung Hoon
AU - Cheong, Jae Ho
N1 - Publisher Copyright:
© Yonsei University College of Medicine 2019.
PY - 2019/2
Y1 - 2019/2
N2 - 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 quasi-monomorphic 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.
AB - 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 quasi-monomorphic 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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U2 - 10.3349/ymj.2019.60.2.132
DO - 10.3349/ymj.2019.60.2.132
M3 - Article
C2 - 30666834
AN - SCOPUS:85060239652
SN - 0513-5796
VL - 60
SP - 132
EP - 139
JO - Yonsei medical journal
JF - Yonsei medical journal
IS - 2
ER -
