INK4家族是细胞周期蛋白依赖性激酶抑制剂(CDKIs)的重要家族,由CDKN2A、CDKN2B,CDKN2和CDKN2D。CDKN2A在肝细胞癌(HCC)中的异常表达已被报道,并且与患者的预后和免疫细胞的浸润有关。然而,缺乏对其他INK4家族成员在诊断中的作用的系统研究,预后,和肝癌的免疫调节。使用在线公共数据库和临床样本,我们全面分析了HCC中的INK4家族。所有四种INK4蛋白均在HCC中过表达,并与晚期癌症分期和不良预后相关。INK4表达准确区分肿瘤与正常组织,特别是CDKN2A和CDKN2C。INK4家族参与细胞周期调控和DNA损伤修复通路,在肿瘤发生中抑制基因毒性诱导的细胞凋亡。INK4蛋白与免疫细胞浸润呈正相关(B细胞、CD8+T细胞,CD4+T细胞,巨噬细胞,中性粒细胞,和树突状细胞)和免疫检查点(CTLA-4,PD1和PD-L1)。CDKN2D与上述所有浸润免疫细胞和免疫检查点的相关性最高(相关系数>0.3)。这表明它可以作为免疫疗法的靶点。INK4家族对HCC的诊断和预后判断具有重要价值,参与了HCC的发生,programming,和肝癌的免疫调节,证明其作为HCC诊断和预后生物标志物和治疗靶点的潜力。
The
INK4 family is an important family of cyclin-dependent kinase inhibitors (CDKIs) and consists of CDKN2A, CDKN2B, CDKN2, and CDKN2D. Abnormal expression of CDKN2A has been reported in hepatocellular carcinoma (HCC) and is associated with the prognosis of patients and infiltration of immune cells. However, there is a lack of systematic research on the roles of the other
INK4 family members in the diagnosis, prognosis, and immune regulation of HCC. Using online public databases and clinical samples, we comprehensively analyzed the
INK4 family in HCC. All four INK4 proteins were overexpressed in HCC and correlated with advanced cancer stage and poor prognosis.
INK4 expression accurately distinguished tumor from normal tissue, particularly CDKN2A and CDKN2C. The INK4 family participated in cell-cycle regulation and the DNA damage repair pathway, which inhibited genotoxic-induced apoptosis in tumorigenesis.
INK4 proteins were positively correlated with the infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) and immune checkpoints (CTLA-4, PD1, and PD-L1). CDKN2D had the highest correlation (correlation coefficient >0.3) with all the above-mentioned infiltrating immune cells and immune checkpoints, indicating that it may be useful as an immunotherapy target. The INK4 family was valuable for diagnosis and predicting the prognosis of HCC and participated in the occurrence, progression, and immune regulation of HCC, demonstrating its potential as a diagnostic and prognostic biomarker and therapeutic target in HCC.