Xiong Jiani, Deng Cuimin, Fu YunRong, Tang Jingji, Xie Jieming, Chen Yu
Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Cancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Mol Biotechnol. 2025 Jun;67(6):2455-2466. doi: 10.1007/s12033-024-01209-3. Epub 2024 Jul 24.
PRKDC is a key factor involved in the ligation step of the non-homologous end joining pathway. Its dysfunction has proven to be a biomarker for radiosensitivity of cancer cells. However, the prognostic value of PRKDC and its underlying mechanisms have not been clarified yet. In this study, we found that PRKDC overexpressed in lung adenocarcinoma (LUAD) and is significantly related to unfavorable survival, while downregulation of PRKDC is link to inflamed tumor immune signature. Our further in vitro results also showed a potent antitumor efficacy of PRKDC inhibitors alone or combined with cisplatin in human lung cancer cells. This study demonstrated that PRKDC is a potential prognostic biomarker, immunotherapy target, and promising combination candidate for chemotherapy for lung cancer, and highlighted the potential of PRKDC-targeted inhibitors for the treatment of lung cancer.
PRKDC是参与非同源末端连接途径连接步骤的关键因素。其功能障碍已被证明是癌细胞放射敏感性的生物标志物。然而,PRKDC的预后价值及其潜在机制尚未阐明。在本研究中,我们发现PRKDC在肺腺癌(LUAD)中过表达,且与不良生存显著相关,而PRKDC的下调与炎症性肿瘤免疫特征有关。我们进一步的体外实验结果还表明,PRKDC抑制剂单独或与顺铂联合使用对人肺癌细胞具有强大的抗肿瘤功效。本研究表明,PRKDC是肺癌潜在的预后生物标志物、免疫治疗靶点和有前景的化疗联合候选药物,并突出了PRKDC靶向抑制剂治疗肺癌的潜力。