当前位置: X-MOL 学术Funct. Integr. Genomics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A prognostic marker LTBP1 is associated with epithelial mesenchymal transition and can promote the progression of gastric cancer
Functional & Integrative Genomics ( IF 2.9 ) Pub Date : 2024-02-15 , DOI: 10.1007/s10142-024-01311-4
Xinju Jiang , Shengjie Yin , Xin Yin , Yufei Wang , Tianyi Fang , Shuo Yang , Xiulan Bian , Guoli Li , Yingwei Xue , Lei Zhang

LTBP1 is closely related to TGF-β1 function as an essential component, which was unclear in gastric cancer (GC). Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined to form a training cohort to calculate the connection between LTBP1 mRNA expression, prognosis and clinicopathological features. The training cohort was also used to verify the biological function of LTBP1 and its relationship with immune microenvironment and chemosensitivity. In the tissue microarrays (TMAs), immunohistochemical (IHC) staining was performed to observe LTBP1 protein expression. The correlation between LTBP1 protein expression level and prognosis was also analyzed, and a nomogram model was constructed. Western blotting (WB) was used in cell lines to assess LTBP1 expression. Transwell assays and CCK-8 were employed to assess LTBP1's biological roles. In compared to normal gastric tissues, LTBP1 expression was upregulated in GC tissues, and high expression was linked to a bad prognosis for GC patients. Based on a gene enrichment analysis, LTBP1 was primarily enriched in the TGF-β and EMT signaling pathways. Furthermore, high expression of LTBP1 in the tumor microenvironment was positively correlated with an immunosuppressive response. We also found that LTBP1 expression (p = 0.006) and metastatic lymph node ratio (p = 0.044) were independent prognostic risk factors for GC patients. The prognostic model combining LTBP1 expression and lymph node metastasis ratio reliably predicted the prognosis of GC patients. In vitro proliferation and invasion of MKN-45 GC cells were inhibited and their viability was decreased by LTBP1 knockout. LTBP1 plays an essential role in the development and progression of GC, and is a potential prognostic biomarker and therapeutic target for GC.



中文翻译:

预后标志物 LTBP1 与上皮间质转化相关,可促进胃癌进展

LTBP1作为必需成分与TGF-β1功能密切相关,但在胃癌(GC)中这一点尚不清楚。哈尔滨医科大学 (HMU)-GC 队列和癌症基因组图谱 (TCGA) 数据集合并形成训练队列,以计算 LTBP1 mRNA 表达、预后和临床病理特征之间的联系。训练队列还用于验证LTBP1的生物学功能及其与免疫微环境和化疗敏感性的关系。在组织微阵列(TMAs)中,进行免疫组织化学(IHC)染色以观察LTBP1蛋白表达。分析LTBP1蛋白表达水平与预后的相关性,并构建列线图模型。在细胞系中使用蛋白质印迹 (WB) 来评估 LTBP1 表达。 Transwell 检测和 CCK-8 用于评估 LTBP1 的生物学作用。与正常胃组织相比,GC组织中LTBP1表达上调,高表达与GC患者的不良预后相关。根据基因富集分析,LTBP1 主要富集于 TGF-β 和 EMT 信号通路。此外,肿瘤微环境中LTBP1的高表达与免疫抑制反应呈正相关。我们还发现LTBP1表达(p  = 0.006)和转移淋巴结比率(p  = 0.044)是GC患者的独立预后危险因素。结合LTBP1表达和淋巴结转移率的预后模型可靠地预测GC患者的预后。 LTBP1 敲除可抑制 MKN-45 GC 细胞的体外增殖和侵袭,并降低其活力。 LTBP1在GC的发生和进展中发挥着重要作用,是GC潜在的预后生物标志物和治疗靶点。

更新日期:2024-02-15
down
wechat
bug