Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
Department of Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2024 Jan;56(1):219-237. doi: 10.4143/crt.2023.340. Epub 2023 Aug 11.
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.
骨转移（BM）会对胃癌（GC）的预后产生不利影响。我们研究了与无 BM 的 GC 相比，具有 BM 的 GC 的分子特征和免疫微环境。
对 50 例有远处转移的 GC 病例（14 例有 BM，36 例无 BM）的福尔马林固定石蜡包埋原发肿瘤组织（胃切除术标本）进行了靶向 DNA 和全转录组测序。此外，还进行了黏蛋白-12 的免疫组化（IHC）和免疫细胞标志物的多重 IHC。
大多数具有 BM 的 GC 病例具有非黏附性癌的组织学类型，总生存（OS）较无 BM 的 GC 差（p < 0.05）。与无 BM 的 GC 相比，BM 的 GC 中 TP53、KDR、APC、KDM5A 和 RHOA 的突变率更高。与无 BM 的 GC 相比，BM 的 GC 中主细胞富集基因（PGA3、PGC 和 LIPF）、MUC12、MFSD4A、TSPAN7 和 TRIM50 上调，与 OS 不良相关（p < 0.05）。然而，BM 的 GC 中 SERPINA6、SLC30A2、PMAIP1 和 ITIH2 的表达下调。BM 的 GC 与 PI3K/AKT/mTOR 通路激活相关，而无 BM 的 GC 则相反。两组之间辅助性、细胞毒性和调节性 T 细胞的密度没有差异，而 BM 的 GC 中的巨噬细胞密度较低（p < 0.05）。
与无 BM 的 GC 相比，具有 BM 的 GC 具有不同的基因突变和表达谱，并且具有更多与不良预后相关的遗传改变。
