Kanda Mitsuro, Murotani Kenta, Tanaka Haruyoshi, Miwa Takashi, Umeda Shinichi, Tanaka Chie, Kobayashi Daisuke, Hayashi Masamichi, Hattori Norifumi, Suenaga Masaya, Yamada Suguru, Nakayama Goro, Fujiwara Michitaka, Kodera Yasuhiro
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan.
Oncotarget. 2018 Apr 10;9(27):18775-18785. doi: 10.18632/oncotarget.24661.
Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506-0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents (, and ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1-3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.
由于胃癌固有的生物学和基因异质性,大多数提出的个体标志物临床应用有限。我们旨在构建一种新的基于分子的模型来预测胃癌患者的预后。共有200例行胃癌胃切除术的患者使用随机数字表按1:1的比例分为学习队列和验证队列。在学习队列中,分析胃组织中15种分子标志物的mRNA表达水平,并计算这15种候选标志物所有单因素及组合因素对总生存的一致性指数(C指数)值。根据C指数值和亚组指数设计多基因表达谱。根据各成分的系数加权确定表达分数。在验证队列中评估该表达谱的可重复性。15种单个候选标志物的C指数值范围为0.506 - 0.653。在32767种组合中,最佳且平衡的表达谱由四个成分(、和)组成,C指数值为0.793。使用该表达谱,患者被临时分为1 - 3分,明显分层为总生存良好、中等和较差组。在验证队列中,总生存率和无病生存率均随着表达分数的增加而逐渐降低。多因素分析显示,表达分数是根治性胃切除术后总生存的独立预后因素。我们开发了一种综合多基因表达谱,可简单、准确地对胃癌患者的风险进行分层。