研究动态
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胶原相关基因表达水平预测预后和免疫治疗反应。

Collagen-related gene expression level predicts the prognosis and immune therapy response.

发表日期:2023 Aug 06
作者: Jianchao Wang, Zhentian Liu, Liyan Lin, Zhida Wu, Xuan Gao, Xiqian Cai, Lianpeng Chang, Xuefeng Xia, Hejun Zhang, Gang Chen
来源: Gastric Cancer

摘要:

由于缺乏生物标志物以指导治疗选择,胃癌患者对相同的治疗策略作出不同反应,并且存在各种预后。我们对一组包含103名患者的胃癌局部RNA数据进行了处理并用于探究潜在的治疗指导因素。我们采用非负矩阵分解进行了聚类分析。使用单一样本基因集富集分析(ssGSEA)评估了与胶原相关基因的表达水平,被称为胶原评分(CS)。利用来自TCGA、ACRG和免疫疗法队列的数据探究预后和疗效。通过利用诊断符图(nomogram)评估了CS的预后预测能力。 在我们的研究中,我们对局部RNA数据进行了聚类分析,并发现聚类2中的肿瘤浸润状态更差。GSEA结果显示,在两个聚类中胶原相关通路的激活水平有所差异。在TCGA和ACRG队列中,CS可以作为独立的预后因素(TCGA OS:p = 0.018,HR = 3.5; ACRG OS:p = 0.014,HR = 4.88)。一个免疫疗法队列显示,CS较高的患者具有显著较差的ORR(p = 0.0025)。高CS组中存在多个细胞死亡通路的下调,并且包含更差的肿瘤微环境。诊断符图展示了胶原评分的生存预测能力。 CS被验证为独立的预后因素,并且可能反映了免疫疗法的治疗效果。CS可以提供一种评估临床预后和响应信息的新方法,并有助于开发以胶原为靶点的治疗方法。 ©2023。本文作者独占许可给国际胃癌协会和日本胃癌协会。
Gastric cancer patients responded differently to the same treatment strategy and had various prognoses for the lack of biomarkers to guide the therapy choice.RNA data of a local gastric cancer cohort with 103 patients were processed and used to explore potential treatment guiding factors. Cluster analysis was performed by non-negative matrix factorization. The expression level of collagen-related genes was evaluated by ssGSEA named collagen score (CS). Data from TCGA, ACRG, and an immune therapy cohort were utilized to explore prognosis and efficacy. Prognostic predictive power of CS was assessed using the nomogram.In our study, local RNA data were processed by cluster analysis, and it was found that cluster 2 contained a worse tumor infiltration status. The GSEA result showed that collagen-related pathways were differentially activated in two clusters. In TCGA and ACRG cohorts, the CS can be used as an independent prognostic factor (TCGA OS: p = 0.018, HR = 3.5; ACRG OS: p = 0.014, HR = 4.88). An immunotherapy cohort showed that the patients with higher CS had a significantly worse ORR (p = 0.0025). The high CS group contained several cell death pathways down-regulated and contained the worse tumor microenvironment. The nomogram demonstrated the survival prediction capability of collagen score.CS was verified as an independent prognostic factor and potentially reflected the therapeutic effect of immunotherapy. The CS could provide a new way to evaluate the clinical prognosis and response information helping develop the collagen-targeted treatment.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.