Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
Department of Surgery, Ozawa Hospital, 1-1-17, Honcho, Odawara, Kanagawa, 250-0012, Japan.
Sci Rep. 2022 May 20;12(1):8509. doi: 10.1038/s41598-022-12439-3.
Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30-0.78]; p < 0.01; interaction p-value < 0.01). This is the first study to identify VSNL1 and CD44 RNA expression levels as biomarkers for selecting GC patients that are likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy. Our findings may facilitate clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for patients with locally advanced GC.
使用 SAMIT 三期随机对照试验中招募的患者的组织样本,研究了用于选择可能从紫杉醇序贯治疗联合氟嘧啶类辅助化疗(序贯紫杉醇)中获益的胃癌(GC)患者的生物标志物。从 556 例 GC 切除样本中提取总 RNA。使用实时 PCR 定量测定 105 个基因的表达。根据与生物标志物和序贯紫杉醇或单药治疗组之间的相互作用相关的 p 值的排名,确定预测序贯紫杉醇对总生存期、无病生存期和复发累积发生率的获益的基因。低 VSNL1 和 CD44 表达预测了所有三个终点的序贯紫杉醇治疗获益。同时这两个基因低表达的患者从序贯紫杉醇治疗中获益最大(风险比=0.48[95%置信区间,0.30-0.78];p<0.01;交互 p 值<0.01)。这是第一项鉴定 VSNL1 和 CD44 RNA 表达水平作为选择可能从紫杉醇序贯治疗联合氟嘧啶类辅助化疗中获益的 GC 患者的生物标志物的研究。我们的发现可能有助于针对局部晚期 GC 患者的基于生物标志物的术后辅助化疗的临床试验。