Department of Pathology, Basic Medical Science College, Harbin Medical University, Harbin, Heilongjiang, China.
Department of Medical Oncology, Municipal Hospital of Chifeng, Chifeng, Inner Mongolia Autonomous Region, China.
Funct Integr Genomics. 2024 Feb 15;24(1):30. doi: 10.1007/s10142-024-01311-4.
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.
LTBP1 作为 TGF-β1 功能的必需组成部分,与胃癌(GC)的关系尚不清楚。哈尔滨医科大学(HMU)-GC 队列和癌症基因组图谱(TCGA)数据集被合并形成一个训练队列,以计算 LTBP1 mRNA 表达与预后和临床病理特征之间的联系。该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(TMA)中,进行免疫组织化学(IHC)染色以观察 LTBP1 蛋白表达。还分析了 LTBP1 蛋白表达水平与预后的相关性,并构建了列线图模型。在细胞系中使用 Western blot(WB)评估 LTBP1 表达。使用 Transwell 测定和 CCK-8 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 患者预后不良相关。基于基因富集分析,LTBP1 主要富集在 TGF-β 和 EMT 信号通路中。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)和转移性淋巴结比率(p=0.044)是 GC 患者独立的预后危险因素。结合 LTBP1 表达和淋巴结转移比率的预后模型可靠地预测了 GC 患者的预后。LTBP1 敲除抑制 MKN-45 GC 细胞的体外增殖和侵袭,并降低其活力。LTBP1 在 GC 的发生和发展中起重要作用,是 GC 的潜在预后生物标志物和治疗靶点。