Development and validation of a prognostic and predictive 32-gene signature for gastric cancer.

Development and validation of a prognostic and predictive 32-gene signature for gastric cancer.
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胃癌预后和预测性32基因标签的开发和验证。

DOI:
10.1038/s41467-022-28437-y
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发表时间:
2022-02-09
影响因子:
16.6
通讯作者:
Hwang TH
Hwang TH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cheong JH;Wang SC;Park S;Porembka MR;Christie AL;Kim H;Kim HS;Zhu H;Hyung WJ;Noh SH;Hu B;Hong C;Karalis JD;Kim IH;Lee SH;Hwang TH

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基因组图谱可以提供预后和预测性信息来指导临床治疗。缺乏可靠地预测患者对化疗和免疫检查点抑制反应的生物标志物。在这项回顾分析中,我们使用我们的机器学习算法NTriPath来识别胃癌特有的32基因签名。通过对567例患者肿瘤中这32个基因的表达水平进行无监督的聚类,我们确定了四种对生存有影响的分子亚型。然后,我们构建了一个线性核的支持向量机来生成一个对五年总存活率具有预测性的风险分数,并使用三个独立的数据集来验证风险分数。我们还发现,分子亚型预测胃切除术后对5-氟尿嘧啶和铂类辅助治疗的反应,以及对转移性或复发性疾病患者免疫检查点抑制剂的反应。综上所述,我们表明,32基因信号是一个有前景的预后和预测性生物标志物,以指导胃癌患者的临床护理,并应以前瞻性的方式使用大的患者队列进行验证。预测癌症患者的生存和治疗反应的能力可能会改善患者的护理。在这里,作者产生了一个32基因信号,可以预测胃癌患者的生存和治疗反应。
Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner. The ability to predict the survival and response to treatment of cancer patients may improve patient care. Here, the authors generate a 32 gene signature that can predict the survival and response to treatment in gastric cancer patients.
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