Department of General Surgery, The First Hospital of China Medical University, Shenyang, China.
Cancer Med. 2023 Apr;12(8):10138-10155. doi: 10.1002/cam4.5718. Epub 2023 Feb 28.
Cell division cycle-associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear.
Herein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT-PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results.
Elevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p < 0.001), disease-specific survival (DSS) (p < 0.001), and progress free interval (PFI) H(p < 0.001). According to the ROC analysis, the area under the curve (AUC) was 0.997. Multivariate analysis revealed that CDCA8 was a stand-alone prognostic indicator of patient OS (p = 0.009) and DSS (p = 0.006). A nomogram was then generated based on the multivariate analysis, and the C-indexes and calibration chart revealed excellent predictive performance in determining HCC patient outcome. Based on the GSEA analysis, CDCA8 modulated the P53, Notch, PPAR, E2F networks. We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Furthermore, CDCA8 deficiency inhibited liver cancer cell proliferation and invasion.
In conclusion, these findings indicate that CDCA8 is a new molecular bioindicator of HCC patient prognosis, and it is an excellent candidate for therapeutic target against HCC.
细胞分裂周期相关蛋白 8（CDCA8）参与了众多信号网络，在多种恶性肿瘤中发挥着关键的调节作用。然而，其在肝细胞癌（HCC）中的预后意义和免疫浸润情况尚不清楚。
本研究检测了肿瘤组织中的 CDCA8 水平，以及其相关的信号通路与免疫浸润的相关性。此外，我们进一步明确了 CDCA8 对 HCC 患者预后的意义。HCC 患者信息取自癌症基因组图谱（TCGA）数据库。采用生物信息学方法，对 HCC 患者的 CDCA8 表达、富集分析、免疫浸润和预后分析等参数进行分析。同时，我们还进行了体外研究，如 qRT-PCR、免疫组织化学（IHC）和细胞功能实验，以验证我们的结果。
CDCA8 在 HCC 患者中的高表达与 T 分期、病理状态（PS）、肿瘤状态（TS）、组织学分级（HG）和 AFP 显著相关。CDCA8 高表达的 HCC 患者的总生存期（OS）（p<0.001）、疾病特异性生存期（DSS）（p<0.001）和无进展生存期（PFI）较短（p<0.001）。ROC 分析显示曲线下面积（AUC）为 0.997。多因素分析显示，CDCA8 是 OS（p=0.009）和 DSS（p=0.006）的独立预后指标。根据多因素分析，我们构建了一个列线图，C 指数和校准图显示了对 HCC 患者预后判断的良好预测性能。基于 GSEA 分析，CDCA8 调节了 P53、Notch、PPAR 和 E2F 网络。我们观察到 CDCA8 水平与 Th2 和辅助性 T 细胞呈正相关，与树突状细胞（DC）、中性粒细胞、细胞毒性细胞和 CD8+T 细胞呈负相关。此外，CDCA8 缺失抑制了肝癌细胞的增殖和侵袭。
综上所述，这些发现表明 CDCA8 是 HCC 患者预后的新分子生物标志物，是治疗 HCC 的潜在靶点。
