Background Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. Methods We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. Results DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). Conclusion These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.

中文翻译：

---

DUSP12调节肝细胞癌的肿瘤发生和预后

背景 双特异性蛋白磷酸酶 (DUSP)12 是蛋白酪氨酸磷酸酶家族的非典型成员，在多种恶性肿瘤中过度表达。该蛋白质家族保护细胞免于凋亡并促进细胞的增殖和运动。然而，DUSP12 在肝细胞癌 (HCC) 中的病理作用尚不完全清楚。方法 我们使用多个在线数据库分析 HCC 和正常肝组织之间的 DUSP12 mRNA 表达，并使用 cBioPortal 数据库探索 DUSP12 突变体的状态。DUSP12 表达与肿瘤浸润免疫细胞之间的相关性通过肿瘤免疫估计资源数据库和肿瘤与免疫系统相互作用数据库得到证实。功能丧失测定法用于评估 DUSP12 在 HCC 进展中的作用。结果与正常肝组织相比，DUSP12在HCC组织中的表达和mRNA扩增均较高，这表明DUSP12较高的表达预示着较短的总生存期。差异表达基因的功能富集分析表明，DUSP12 调节 HCC 肿瘤发生，短发夹 (sh)RNA 敲低 DUSP12 表达降低了 HCC 细胞的增殖和迁移。此外，DUSP12的表达与分化簇（CD）4+ T细胞（尤其是CD4+调节性T细胞）、巨噬细胞、中性粒细胞和树突状细胞的浸润呈正相关。DUSP12 表达与免疫检查点部分呈正相关，并且在 HCC 的 C3 免疫亚组中下调（存活时间最长）。结论 这些数据表明DUSP12可能在HCC的肿瘤发生、免疫细胞浸润和预后中发挥关键作用。