SH2D1A 的过表达通过生物信息学和体外研究促进肝癌的癌症进展，并与肝癌免疫细胞浸润相关。
Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
机构信息
Department of Cardiothoracic surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
出版信息
BMC Cancer. 2023 Oct 19;23(1):1005. doi: 10.1186/s12885-023-11315-1.
BACKGROUND
SH2 domain containing 1A (SH2D1A) expression has been linked to cancer progression. However, the functions of SH2D1A in hepatocellular carcinoma (HCC) have not been reported.
METHODS
The effects of SH2D1A on the proliferation, migration, and invasion of HCC cells and the related pathways were re-explored in cell models with SH2D1A overexpression using the CCK-8, migration and invasion assays and western blotting. The functions and mechanisms of genes co-expressed with SH2D1A were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between SH2D1A expression and immune microenvironment features in HCC was explored.
RESULTS
Elevated SH2D1A expression promoted cell proliferation, migration, and invasion, which was related to the overexpression of p-Nf-κB and BCL2A1 protein levels in HCC. SH2D1A expression was related to the immune, stromal, and ESTIMATE scores, and the abundance of immune cells, such as B cells, CD8 T cells, and T cells. SH2D1A expression was significantly related to the expression of immune cell markers, such as PDCD1, CD8A, and CTLA4 in HCC.
CONCLUSION
SH2D1A overexpression was found to promote cell growth and metastasis via the Nf-κB signaling pathway and may be related to the immune microenvironment in HCC. The findings indicate that SH2D1A can function as a biomarker in HCC.
背景
SH2 结构域包含 1A（SH2D1A）的表达与癌症进展有关。然而，SH2D1A 在肝细胞癌（HCC）中的功能尚未报道。
方法
在过表达 SH2D1A 的细胞模型中，使用 CCK-8、迁移和侵袭实验以及 Western blot 重新探讨 SH2D1A 对 HCC 细胞增殖、迁移和侵袭的影响及其相关途径。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析分析与 SH2D1A 共表达的基因的功能和机制。探讨 SH2D1A 表达与 HCC 免疫微环境特征的关系。
结果
升高的 SH2D1A 表达促进了 HCC 细胞的增殖、迁移和侵袭，这与 p-Nf-κB 和 BCL2A1 蛋白水平的过表达有关。SH2D1A 表达与免疫、基质和 ESTIMATE 评分以及 B 细胞、CD8 T 细胞和 T 细胞等免疫细胞的丰度有关。SH2D1A 表达与 HCC 中免疫细胞标志物的表达，如 PDCD1、CD8A 和 CTLA4 显著相关。
结论
过表达 SH2D1A 通过 Nf-κB 信号通路促进细胞生长和转移，并且可能与 HCC 的免疫微环境有关。这些发现表明 SH2D1A 可以作为 HCC 的标志物。
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