骨转移（BM）对胃癌（GC）的预后产生不利影响。我们比较了具有BM的GC与没有BM的GC之间的分子特征和免疫微环境。使用固定在福尔马林和石蜡中的原发肿瘤组织（胃切除标本），对50例有远处转移的GC病例进行了定向DNA和全转录组测序（其中14例有BM，36例没有BM）。此外，进行了黏附-12的免疫组化和免疫细胞标记物的多重免疫组化检测。大多数具有BM的GC病例具有差异性癌组织学类型，并显示出比没有BM的GC预后更差（p<0.05）。与没有BM的GC相比，GC具有BM的突变率在TP53、KDR、APC、KDM5A和RHOA方面更高。与没有BM的GC相比，GC具有BM的PGA3、PGC和LIPF这些主要细胞富集基因，以及MUC12、MFSD4A、TSPAN7和TRIM50在表达上升，且与不良预后相关（p<0.05）。然而，在GC具有BM的情况下，SERPINA6、SLC30A2、PMAIP1和ITIH2的表达下调。GC具有BM与PIK3/AKT/mTOR通路的激活相关，而没有BM的GC则显示相反的效应。辅助T细胞、细胞毒性T细胞和调节性T细胞的密度在这两组之间没有差异，而巨噬细胞的密度在具有BM的GC中较低（p<0.05）。GC具有BM与没有BM的GC相比，基因突变和表达谱不同，并且具有更多与不良预后相关的遗传改变。

Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p<0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p<0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p<0.05).GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.