CDKL3 是一种有前景的肝细胞癌诊断和预后预测生物标志物。
CDKL3 is a promising biomarker for diagnosis and prognosis prediction in patients with hepatocellular carcinoma.
发表日期:2024
作者:
Qingsi Wu, Mengran Lu, Huijuan Ouyang, Tingting Zhou, Jingyuan Lei, Panpan Wang, Wei Wang
来源:
Parasites & Vectors
摘要:
细胞周期蛋白依赖性激酶样 3 (CDKL3) 已被确定为某些类型肿瘤中的癌基因。尽管如此,其在肝细胞癌(HCC)中的功能仍知之甚少。在本研究中,我们根据癌症基因组图谱 (TCGA) HCC 队列的数据对 CDKL3 进行了全面分析。我们的分析包括基因表达、诊断、预后、功能富集、肿瘤微环境和代谢特征、肿瘤负荷、基于 mRNA 表达的干性、选择性剪接和治疗反应预测。此外,我们还进行了细胞计数试剂盒8测定、TdT介导的dUTP缺口末端标记染色、迁移测定、伤口愈合测定、集落形成测定和裸鼠实验,以确认CDKL3在HCC中的功能相关性。我们的研究结果表明,与对照组相比,HCC 患者的 CDKL3 显着上调。各种生物信息分析表明CDKL3可以作为HCC诊断和预后的潜在标志物。此外,CDKL3被发现参与与HCC发展相关的多种机制,包括拷贝数变异、肿瘤负荷、基因组异质性、癌症干性和CDKL3的选择性剪接。值得注意的是,CDKL3还与肿瘤免疫细胞浸润和免疫检查点标志物的表达密切相关。此外,多变量 Cox 回归分析表明,CDKL3 可独立作为 HCC 患者总体生存的风险预测因子。此外,CDKL3 的敲低在体外和体内均显着抑制细胞增殖,表明其在 HCC 中作为癌基因的作用。总而言之,我们的研究结果表明 CDKL3 作为 HCC 患者检测和治疗结果预测的生物标志物具有前景。版权所有 © 2024 Wu、Lu、Ouyang、Zhou、Lei、Wang 和 Wang。
Cyclin-dependent kinase-like 3 (CDKL3) has been identified as an oncogene in certain types of tumors. Nonetheless, its function in hepatocellular carcinoma (HCC) is poorly understood. In this study, we conducted a comprehensive analysis of CDKL3 based on data from the HCC cohort of The Cancer Genome Atlas (TCGA). Our analysis included gene expression, diagnosis, prognosis, functional enrichment, tumor microenvironment and metabolic characteristics, tumor burden, mRNA expression-based stemness, alternative splicing, and prediction of therapy response. Additionally, we performed a cell counting kit-8 assay, TdT-mediated dUTP nick-end Labeling staining, migration assay, wound healing assay, colony formation assay, and nude mouse experiments to confirm the functional relevance of CDKL3 in HCC. Our findings showed that CDKL3 was significantly upregulated in HCC patients compared to controls. Various bioinformatic analyses suggested that CDKL3 could serve as a potential marker for HCC diagnosis and prognosis. Furthermore, CDKL3 was found to be involved in various mechanisms linked to the development of HCC, including copy number variation, tumor burden, genomic heterogeneity, cancer stemness, and alternative splicing of CDKL3. Notably, CDKL3 was also closely correlated with tumor immune cell infiltration and the expression of immune checkpoint markers. Additionally, CDKL3 was shown to independently function as a risk predictor for overall survival in HCC patients by multivariate Cox regression analysis. Furthermore, the knockdown of CDKL3 significantly inhibited cell proliferation in vitro and in vivo, indicating its role as an oncogene in HCC. Taken together, our findings suggest that CDKL3 shows promise as a biomarker for the detection and treatment outcome prediction of HCC patients.Copyright © 2024 Wu, Lu, Ouyang, Zhou, Lei, Wang and Wang.