Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Department of Gynocology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Medicine (Baltimore). 2022 Jul 8;101(27):e29628. doi: 10.1097/MD.0000000000029628.
While protein kinase, DNA-activated, catalytic subunit (PRKDC) plays an important role in double-strand break repair to retain genomic stability, there is still no pan-cancer analysis based on large clinical information on the relationship between PRKDC and different tumors. For the first time, this research used numerous databases to perform a pan-cancer review for PRKDC to explore the possible mechanism of PRKDC in the etiology and outcomes in various tumors.
PRKDC's expression profile and prognostic significance in pan-cancer were investigated based on various databases and online platforms, including TIMER2, GEPIA2, cBioPortal, CPTAC, and SangerBox. We applied the TIMER to identified the interlink of PRKDC and the immune infiltration in assorted tumors, and the SangerBox online platform was adopted to find out the relevance between PRKDC and immune checkpoint genes, tumor mutation burden, and microsatellite instability in tumors. GeneMANIA tool was employed to create a protein-protein interaction analysis, gene set enrichment analysis was conducted to performed gene enrichment analysis.
Overall, tumor tissue presented a higher degree of PRKDC expression than adjacent normal tissue. Meanwhile, patients with high PRKDC expression have a worse prognosis. PRKDC mutations were present in almost all The Cancer Genome Atlas tumors and might lead to a better survival prognosis. The PRKDC expression level was shown a positive correlation with tumor-infiltrating immune cells. PRKDC high expression cohorts were enriched in "cell cycle" "oocyte meiosis" and "RNA-degradation" signaling pathways.
This study revealed the potential value of PRKDC in tumor immunology and as a therapeutic target and prognostic biomarker in pan-cancer.
蛋白激酶 DNA 激活催化亚基（PRKDC）在双链断裂修复中发挥重要作用，以保持基因组稳定性，但基于大量临床信息，尚无关于 PRKDC 与不同肿瘤之间关系的泛癌分析。本研究首次利用多个数据库对 PRKDC 进行泛癌综述，以探讨 PRKDC 在各种肿瘤病因和结局中的可能机制。
基于 TIMER2、GEPIA2、cBioPortal、CPTAC 和 SangerBox 等多种数据库和在线平台，研究 PRKDC 在泛癌中的表达谱和预后意义。我们应用 TIMER 鉴定 PRKDC 与各种肿瘤中免疫浸润的相互关系，利用 SangerBox 在线平台找出 PRKDC 与免疫检查点基因、肿瘤突变负荷和肿瘤微卫星不稳定性之间的相关性。采用 GeneMANIA 工具进行蛋白质-蛋白质相互作用分析，进行基因富集分析。
总体而言，肿瘤组织中 PRKDC 的表达程度高于相邻正常组织。同时，PRKDC 高表达的患者预后较差。几乎所有癌症基因组图谱肿瘤都存在 PRKDC 突变，可能导致更好的生存预后。PRKDC 的表达水平与肿瘤浸润免疫细胞呈正相关。PRKDC 高表达队列富集在“细胞周期”“卵母细胞减数分裂”和“RNA 降解”信号通路中。
本研究揭示了 PRKDC 在肿瘤免疫学中的潜在价值，以及作为泛癌治疗靶点和预后生物标志物的潜力。
