Data_Sheet_3_Identification of a Hypoxia-Related Gene Signature for Predicting Systemic Metastasis in Prostate Cancer.XLS

Background: 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.
Methods: 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 ALDOB 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.
Results: The hypoxia-related gene signature was identified as an independent risk factor for metastasis-free survival in patients with prostate cancer. The expression of ALDOB 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.
Conclusion: 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.

背景：远处转移是前列腺癌患者死亡的主要诱因。亟需构建更为精准的预测模型，以甄别转移高风险患者并预判其转移风险，进而优化个体化治疗策略。方法：本研究证实缺氧可显著影响前列腺癌患者的无转移生存时长；据此构建了由7个基因组成的缺氧相关基因特征（hypoxia-related gene signature），用于预测前列腺癌转移风险，并在多独立队列中完成验证。本研究进一步评估了缺氧微环境下ALDOB表达对LNCaP与DU145细胞系增殖及侵袭能力的调控作用；最终结合前列腺癌特异性临床特征与该缺氧基因特征，构建了量化个体患者转移风险的列线图（nomogram）。结果：该缺氧相关基因特征被证实为前列腺癌患者无转移生存的独立危险因素。缺氧条件下ALDOB表达水平显著上调，可促进LNCaP与DU145细胞的增殖与侵袭能力。此外，高风险评分患者呈现治疗抵抗与免疫抑制表型。相较于其他临床参数，该列线图展现出最优的预测效能与净临床获益。结论：本研究成功构建了缺氧相关基因特征与列线图，可有效甄别并预测前列腺癌转移高风险患者，或可为优化个体化治疗方案及探索潜在治疗靶点提供理论依据与实践参考。