RESUMO
BACKGROUND: The proteins CDK4 and CDK6, which are extremely homologous, control cell cycle entry. For the treatment of breast tumors that include hormone receptors, CDK4 and CDK6 inhibitors have been authorized. The link between CDK4 and liver hepatocellular carcinoma (LIHC), however, has not yet been established. OBJECTIVE: The study aimed to explore the link between CDK4 and LIHC and the effect of CDK4 inhibitors on LIHC. METHOD: In this study, we have evaluated CDK4's prognostic relevance in LIHC using data from The Cancer Genome Atlas (TCGA). The relationship between clinical-pathologic features and CDK4 expression has been evaluated using the Kruskal-Wallis test, the Wilcoxon signed-rank test, and logistic regression. We have analyzed CDK4 and factors related to the prognosis of HCC using the Kaplan-Meier technique and multivariate Cox regression. Gene set enrichment analysis (GSEA) identified CDK4-related critical pathways. To investigate the connections between CDK4 and cancer immune infiltrates, TCGA data were employed in single-sample gene set enrichment analysis (ssGSEA). For functional validation, CDK4 was chosen since it can be inhibited by recognized CDK4/ 6-inhibitors (e.g., abemaciclib). RESULTS: Poorer overall and disease-specific outcomes were linked to high CDK4 expression in HCC patients. GSEA suggested that CDK4 and immune response are closely connected. The amount of Th2 cells infiltrating was positively correlated with CDK4 expression, while the amount of cytotoxic cells infiltrating was negatively correlated, according to ssGSEA. Both in vitro and in vivo, the anti-tumor efficacy of CDK4 inhibitor has been found to be superior to that of sorafenib. CONCLUSION: This study suggests a relationship between CDK4 and immune infiltration and prognosis in HCC. Additionally, a CDK4 inhibitor may have anti-tumor properties against hepatocellular cancer.
RESUMO
PURPOSE: Hepatocellular carcinoma (HCC) is a histological type of primary liver cancer, with high recurrence and mortality rates worldwide. At the moment, there are no diagnostic and prognostic markers. microRNAs (miRs) are short-chain non-coding RNAs, and play a vital role in tumor diagnosis and prognosis. METHODS: The miR-187 and miR-509-3p expression in primary HCC was evaluated via qRT-PCR and starBase, and the diagnostic and prognostic values were analyzed via receiver operating characteristic (ROC) curve and Kaplan-Meier method. RESULTS: qRT-PCR and starBase analysis showed that the miR-187 expression was low in the tissues and serum of primary HCC patients, while that of miR-509-3p increased. ROC analysis manifested that the area under the curves (AUCs) of miR-187 and miR-509-3p in primary HCC were 0.842 and 0.866, respectively, and that of joint diagnosis was > 0.9. The 5-year survival rates of miR-187 low expression group and miR-509-3p high expression group decreased markedly. Cox regression analysis identified that pathological differentiation, clinical stage and miR-187 were independent prognostic factors of primary HCC patients. CONCLUSION: miR-187 and miR-509-3p.
