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低 CBS 表达可识别出胃癌患者中从辅助化疗中获益的人群。

Low CBS expression can identify patients who benefit from adjuvant chemotherapy in gastric cancer.

机构信息

Department of Famous Chinese Medicine, Tianjin Nankai Hospital, Tianjin, China.

Department of Rehabilitation, First Teaching Hospital of Tianjin University of TCM, Tianjin, China.

出版信息

Expert Rev Anticancer Ther. 2021 Nov;21(11):1287-1298. doi: 10.1080/14737140.2021.1962298. Epub 2021 Aug 17.

Abstract

To explore the clinical significance of Cystathionine beta-synthase (CBS) expression in gastric cancer (GC). CBS expression and clinicopathological/follow-up information of patients with gastric cancer undergoing operation were collected from The Cancer Genome Atlas (TCGA) database. The association of CBS expression with patients' overall survival (OS) was determined in the entire cohort and different subgroups. Validation was performed in two external cohorts from NCBI Gene Expression Omnibus (GEO) database. The estimated drug response of the tumors with different CBS expressions was characterized. The potential CBS-related cellular pathways in chemoresistance were explored. High CBS was associated with poor OS in patients receiving adjuvant chemotherapy (ACT) but not those without ACT. And ACT was associated with favorable OS in patients with low CBS expression but not those with high CBS expression. The results were verified in two external cohorts. Drug response prediction suggested that patients with low CBS expression showed high sensitivity to 5-Fluorouracil. Gene Set Enrichment Analysis (GSEA) suggested that CBS might contribute to GC chemoresistance via modulating many cellular pathways, including down-regulating apoptosis and P53 pathways while up-regulating DNA repair pathway. Low CBS expression can predict the benefit from ACT in GC.

摘要

探讨半胱氨酸β-合酶(CBS)在胃癌(GC)中的表达的临床意义。从癌症基因组图谱(TCGA)数据库中收集接受手术的胃癌患者的 CBS 表达和临床病理/随访信息。在整个队列和不同亚组中确定 CBS 表达与患者总生存(OS)的关联。在 NCBI 基因表达综合数据库(GEO)中的两个外部队列中进行验证。对不同 CBS 表达的肿瘤的估计药物反应进行了特征描述。探讨了与化疗耐药相关的潜在 CBS 相关细胞途径。高 CBS 与接受辅助化疗(ACT)的患者的 OS 不良相关,但与无 ACT 的患者无关。而 ACT 与低 CBS 表达的患者的良好 OS 相关,但与高 CBS 表达的患者无关。这些结果在两个外部队列中得到了验证。药物反应预测表明,低 CBS 表达的患者对 5-氟尿嘧啶具有高敏感性。基因集富集分析(GSEA)表明,CBS 可能通过调节许多细胞途径,包括下调凋亡和 P53 途径,同时上调 DNA 修复途径,从而导致 GC 化疗耐药。低 CBS 表达可预测 GC 中 ACT 的获益。

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