Department of Gastrointestinal Surgery, Guangxi Medical University Affiliated Tumor Hospital, Guangxi Clinical Research Center for Colorectal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20204359.
We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC).
The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis.
The Log rank test with both Cox regression and Kaplan-Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients.
In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis.
我们旨在探讨解整合素金属蛋白酶与凝血酶样金属蛋白酶（ADAMTS）基因在胃癌（GC）中的预后价值。
从癌症基因组图谱（TCGA）中获取了 351 名 GC 患者的 RNA 测序（RNA-seq）表达数据和其他相关临床数据。进行生存分析和全基因组基因集富集分析（GSEA），以确定 ADAMTS 基因在 GC 发展中的潜在分子价值。此外，还采用 qRT-PCR 和免疫组织化学法验证了这些基因的表达与 GC 患者预后之间的关系。
Cox 回归和 Kaplan-Meier 生存分析的对数秩检验显示，ADAMTS6 表达谱与 GC 患者的临床结局相关。ADAMTS6 高表达的患者总生存期（OS）较差。ADAMTS 基因的综合生存分析表明，ADAMTS6 可能是 GC 患者 OS 的独立预测因子。此外，GSEA 表明，ADAMTS6 可能参与多个生物学过程和途径，如血管内皮生长因子 A（VEGFA）、 Kirsten 大鼠肉瘤病毒癌基因（KRAS）、肿瘤蛋白 P53、c-Jun N-末端激酶（JNK）、钙粘蛋白（CDH1）或肿瘤坏死因子（TNF）途径。免疫组织化学法和 qRT-PCR 也证实了 ADAMTS6 在 GC 中高表达，这可能与 GC 患者的预后有关。
综上所述，我们的研究表明，ADAMTS6 基因可以作为 GC 预后的潜在分子标志物。
