胃癌（GC）具有高度异质性且容易发生转移，这阻碍了治疗的有效性。基底膜（BM）充当肿瘤细胞侵袭和转移的屏障。研究 BM 状态、转移和患者预后之间的关系至关重要。在几个大型队列中，我们研究了基于 BM 基因表达的 GC 分子分类和风险预后模型，检查了不同分子亚型之间的肿瘤微环境 (TME) 差异，并开发了预测预后、免疫治疗有效性和化疗耐药性的风险模型。发现了基于 BM 基因表达状态的三种 GC 亚型（BMclusterA/B/C）。三种 GC 亚型均具有独特的免疫浸润和激活的致癌信号。此外，还开发了 6 基因评分 (BMscore) 预测模型。低BMscore组具有高肿瘤突变负荷、高免疫原性和低RHOJ表达水平，这意味着患有此类GC的个体可能更容易受到免疫疗法和治疗的影响。在亚洲癌症研究组织 (ACRG) 分子分类中，EMT 亚型的 BMscore 显着高于其他亚型。根据单细胞转录组分析，内皮细胞、平滑肌细胞和成纤维细胞可能参与调节 GC 进展中的 BM 重组。总之，我们基于 BM 基因定义了一种新的 GC 分子分类，开发了预后风险模型，并在单细胞水平阐明了参与 BM 重塑的细胞亚群。这项研究加深了对GC转移与BM改变之间关系的理解，实现了预后分层和指导治疗。© 2024。作者。

Gastric cancer (GC) is highly heterogeneous and prone to metastasis, which are obstacles to the effectiveness of treatment. The basement membrane (BM) acts as a barrier to tumor cell invasion and metastasis. It is critical to investigate the relationship between BM status, metastasis, and patient prognosis. In several large cohorts, we investigated BM gene expression-based molecular classification and risk-prognosis models for GC, examined tumor microenvironment (TME) differences among different molecular subtypes, and developed risk models in predicting prognosis, immunotherapy effectiveness, and chemotherapy resistance. Three GC subtypes (BMclusterA/B/C) based on BM gene expression status were discovered. Each of the three GC subtypes has unique immune infiltration and activated oncogenic signals. Moreover, a 6-gene score (BMscore) predictive model was developed. The low BMscore group had a high tumor mutation burden, high immunogenicity, and low RHOJ expression levels, implying that individuals with GC in this category may be more susceptible to immunotherapy and treatment. The EMT subtype showed a considerably higher BMscore than the other subtypes in the Asian Organization for Research on Cancer (ACRG) molecular classification. Endothelial cells, smooth muscle cells, and fibroblasts may be engaged in regulating BM reorganization in GC progression, according to single-cell transcriptome analyses. In conclusion, we defined a novel molecular classification of GC based on BM genes, developed a prognostic risk model, and elucidated the cell subpopulations involved in BM remodeling at the single-cell level. This study has deepened the understanding of the relationship between GC metastasis and BM alterations, achieved prognostic stratification, and guided therapy.© 2024. The Author(s).