The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guiping People's Hospital, Guangxi, China.
Sci Rep. 2024 Mar 7;14(1):5665. doi: 10.1038/s41598-024-55455-1.
Pyruvate dehydrogenase kinases (PDKs) play a key role in glucose metabolism by exerting negative regulation over pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibition of PDKs holds the potential to enhance PDC activity, prompting cells to adopt a more aerobic metabolic profile. Consequently, PDKs emerge as promising targets for condition rooted in metabolic dysregulation, including malignance and diabetes. However, a comprehensive exploration of the distinct contribution of various PDK family members, particularly PDK3, across diverse tumor types remain incomplete. This study undertakes a systematic investigation of PDK family expression patterns, forging association with clinical parameters, using data from the TCGA and GTEx datasets. Survival analysis of PDKs is executed through both Kaplan-Meier analysis and COX regression analysis. Furthermore, the extent of immune infiltration is assessed by leveraging the CIBERSORT algorithm. Our study uncovers pronounced genetic heterogeneity among PDK family members, coupled with discernible clinical characteristic. Significantly, the study establishes the potential utility of PDK family genes as prognostic indicators and as predictors of therapeutic response. Additionally, our study sheds light on the immune infiltration profile of PDK family. The results showed the intimate involvement of these genes in immune-related metrics, including immune scoring, immune subtypes, tumor-infiltrating lymphocytes, and immune checkpoints expression. In sum, the findings of this study offer insightful strategies to guide the therapeutic direction, aiming at leveraging the impact of PDK family genes in cancer treatment.
丙酮酸脱氢酶激酶（PDKs）通过磷酸化对丙酮酸脱氢酶复合物（PDC）活性进行负调控，在葡萄糖代谢中发挥关键作用。抑制 PDKs 有可能增强 PDC 活性，促使细胞采用更有氧的代谢特征。因此，PDKs 成为代谢失调相关疾病（包括恶性肿瘤和糖尿病）的有前途的治疗靶点。然而，对于不同 PDK 家族成员（尤其是 PDK3）在各种肿瘤类型中的独特作用，仍缺乏全面的探索。本研究通过 TCGA 和 GTEx 数据集，系统地研究了 PDK 家族的表达模式，与临床参数建立关联。通过 Kaplan-Meier 分析和 COX 回归分析对 PDKs 进行生存分析。此外，通过 CIBERSORT 算法评估免疫浸润程度。我们的研究揭示了 PDK 家族成员之间存在明显的遗传异质性，并伴有明显的临床特征。值得注意的是，该研究确定了 PDK 家族基因作为预后指标和治疗反应预测因子的潜在应用价值。此外，我们的研究还揭示了 PDK 家族的免疫浸润特征。结果表明这些基因与免疫相关指标密切相关，包括免疫评分、免疫亚型、肿瘤浸润淋巴细胞和免疫检查点表达。总之，这项研究的结果为指导治疗方向提供了有价值的策略，旨在利用 PDK 家族基因在癌症治疗中的影响。
