Table_2_A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC.xlsx

Decaprenyl diphosphate synthase subunit 1 (PDSS1) is closely related to a variety of human diseases, but its expression pattern and biological function in HCC have not been studied to date.
MethodsThe expression level of PDSS1 was analyzed using the TCGA and GEO databases. The relationships between PDSS1 and patient clinicopathological characteristics were verified based on TCGA clinical data. Additionally, the co-expressed genes of PDSS1were investigated and Gene Set Enrichment Analysis (GSEA) was conducted using LinkedOmics. Next, the association between PDSS1 and immune infiltration was determined using version 1.34.0 of the GSVA package. EdU assay, colony-formation assay, transwell assay, wound-healing assay, and flow cytometry analysis were used to assess the effect of PDSS1 on the cell phenotype.
ResultsPDSS1 was upregulated in HCC compared with adjacent tissues. High PDSS1 in HCC was associated with poor overall survival, disease-specific survival, and progress-free interval. Results suggested that PDSS1 may activate multiple oncogenic pathways in HCC, especially those involved in the cell cycle. The expression of PDSS1 was significantly related to Th2 cells, TFH, T helper cells, NK CD56bright cells, cytotoxic cells, DC, CD8 T cells, and neutrophils. PDSS1 knockdown inhibited cell proliferation, cell cycle, migration and invasion. Furthermore, PDSS1 acted as an oncogene through the STAT3 signaling pathway.
ConclusionOur study reveals that a high level of PDSS1 is significantly correlated with poor patient prognosis and immune cell infiltration in HCC. PDSS1 may be a novel biomarker and potential therapeutic target for HCC.

癸异戊烯基二磷酸合酶亚基1（PDSS1）与多种人类疾病密切相关，但截至目前，其在肝细胞癌（Hepatocellular Carcinoma, HCC）中的表达模式与生物学功能尚未得到研究。
方法：本研究利用癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因表达综合数据库（Gene Expression Omnibus, GEO）分析PDSS1的表达水平；基于TCGA临床数据验证PDSS1与患者临床病理特征的关联。此外，本研究通过LinkedOmics工具探究PDSS1的共表达基因，并开展基因集富集分析（Gene Set Enrichment Analysis, GSEA）。随后，使用版本1.34.0的基因集变异分析（Gene Set Variation Analysis, GSVA）包分析PDSS1与免疫浸润的相关性。采用5-乙炔基-2'-脱氧尿苷（EdU）增殖实验、集落形成实验、Transwell实验、划痕愈合实验及流式细胞术分析，评估PDSS1对细胞表型的影响。
结果：与癌旁组织相比，PDSS1在肝细胞癌组织中表达上调。肝细胞癌组织中高表达PDSS1与患者较差的总生存期、疾病特异性生存期及无进展间期显著相关。研究结果提示，PDSS1可能在肝细胞癌中激活多条致癌通路，尤其是参与细胞周期调控的通路。PDSS1的表达与Th2细胞、滤泡辅助性T细胞（TFH）、辅助性T细胞、NK CD56bright细胞、细胞毒性细胞、树突状细胞（DC）、CD8 T细胞及中性粒细胞显著相关。敲低PDSS1可抑制细胞增殖、细胞周期进程、迁移与侵袭。此外，PDSS1可通过信号转导与转录激活因子3（STAT3）信号通路发挥致癌基因作用。
结论：本研究揭示，肝细胞癌组织中PDSS1高表达与患者不良预后及免疫细胞浸润显著相关。PDSS1有望成为肝细胞癌的新型生物标志物与潜在治疗靶点。