PDF(Pubmed)
Abstract：
Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality rates. Molecular targeted therapies, including those targeting human epidermal factor receptor 2 (HER2), have proven to be effective in clinical treatment. However, better identification and description of tumor-promoting genes in GC is still necessary for antitumor therapy. Methods: Gene expression and clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Last absolute shrinkage and selection operator (LASSO) Cox regression were applied to build a prognostic model, the Prognosis Score. Functional enrichment and single-sample gene set enrichment analysis (ssGSEA) were used to explore potential mechanisms. Western blotting, RNA interference, cell migration, and wound healing assays were used to detect the expression and function of myosin light chain 9 (MYL9) in GC. Results: A four-gene prognostic model was constructed and GC patients from TCGA and meta-GEO cohorts were stratified into high-prognosis score groups or low-prognosis score groups. GC patients in the high-prognosis score group had significantly poorer overall survival (OS) than those in the low-prognosis score groups. The GC prognostic model was formulated as PrognosisScore = (0.06 × expression of BGN) - (0.008 × expression of ATP4A) + (0.12 × expression of MYL9) - (0.01 × expression of ALDH3A1). The prognosis score was identified as an independent predictor of OS. High expression of MYL9, the highest weighted gene in the prognosis score, was correlated with worse clinical outcomes. Functional analysis revealed that MYL9 is mainly associated with the biological function of epithelial-mesenchymal transition (EMT). Knockdown of MYL9 expression inhibits migration of GC cells in vitro. Conclusion: We found that PrognosisScore is potential reliable prognostic marker and verified that MYL9 promotes the migration and metastasis of GC cells.
摘要：
背景:胃癌(GC)是一种发病率和死亡率较高的消化系统肿瘤。分子靶向治疗,包括那些靶向人类表皮因子受体2（HER2），在临床治疗中被证明是有效的。然而,在GC中更好地识别和描述肿瘤促进基因对于抗肿瘤治疗仍然是必要的。方法：从癌症基因组图谱（TCGA）和基因表达综合（GEO）数据库下载GC患者的基因表达和临床数据。最后绝对收缩和选择算子(LASSO)Cox回归用于建立预后模型，预后评分。使用功能富集和单样品基因集富集分析（ssGSEA）来探索潜在的机制。西方印迹,RNA干扰,细胞迁移，和伤口愈合试验用于检测肌球蛋白轻链9（MYL9）在GC中的表达和功能。结果：构建了一个四基因预后模型，将来自TCGA和meta-GEO队列的GC患者分为高预后评分组或低预后评分组。高预后评分组的GC患者的总体生存率（OS）明显低于低预后评分组。GC预后模型为预后评分=（BGN的0.06×表达）-（ATP4A的0.008×表达）（MYL9的0.12×表达）-（ALDH3A1的0.01×表达）。预后评分被确定为OS的独立预测因子。MYL9高表达，是预后评分加权最高的基因，与较差的临床结局相关。功能分析显示MYL9主要与上皮间质转化(EMT)的生物学功能有关。MYL9表达的敲低在体外抑制GC细胞的迁移。结论：我们发现PrognosisScore是潜在可靠的预后标志物，并验证了MYL9促进GC细胞的迁移和转移。
