Xia Haoran, Wang Jianlong, Guo Xiaoxiao, Lv Zhengtong, Liu Jingchao, Yan Qiuxia, Liu Ming, Wang Jianye
Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Cell Dev Biol. 2021 Oct 13;9:696364. doi: 10.3389/fcell.2021.696364. eCollection 2021.
Systemic metastasis is the main cause of death in patients with prostate cancer. It is necessary to establish a more accurate model to distinguish and predict patients with a high risk of metastasis to optimize individualized treatment. In this study, it was determined that hypoxia could affect the metastasis-free survival of patients with prostate cancer, and a hypoxia-related gene signature composed of seven genes for predicting metastasis was established and verified in different cohorts. The study further evaluated the effects of expression on the proliferation and invasion of the LNCaP and DU145 cell lines under hypoxia and finally constructed a nomogram containing specific clinical characteristics of prostate cancer combined with the hypoxia gene signature to quantify the metastasis risk of individual patients. The hypoxia-related gene signature was identified as an independent risk factor for metastasis-free survival in patients with prostate cancer. The expression of increased under hypoxia and promoted the proliferation and invasion of LNCaP and DU145 cells. In addition, patients with a high risk score showed therapeutic resistance and immunosuppression. Compared with other parameters, the nomogram had the strongest predictive power and net clinical benefit. The study established a hypoxia-related gene signature and a nomogram to distinguish and predict patients with a high risk of prostate cancer metastasis, which may help to optimize individualized treatment and explore possible therapeutic targets.
全身转移是前列腺癌患者死亡的主要原因。有必要建立一个更准确的模型来区分和预测具有高转移风险的患者，以优化个体化治疗。在本研究中，确定缺氧可影响前列腺癌患者的无转移生存期，并在不同队列中建立并验证了一个由七个基因组成的用于预测转移的缺氧相关基因特征。该研究进一步评估了缺氧条件下该基因表达对LNCaP和DU145细胞系增殖和侵袭的影响，最终构建了一个结合缺氧基因特征和前列腺癌特定临床特征的列线图，以量化个体患者的转移风险。缺氧相关基因特征被确定为前列腺癌患者无转移生存期的独立危险因素。该基因在缺氧条件下表达增加，促进了LNCaP和DU145细胞的增殖和侵袭。此外，高风险评分的患者表现出治疗抵抗和免疫抑制。与其他参数相比，列线图具有最强的预测能力和净临床获益。该研究建立了缺氧相关基因特征和列线图来区分和预测前列腺癌高转移风险患者，这可能有助于优化个体化治疗并探索潜在的治疗靶点。
