Core Laboratory, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan 030012, China.
Aging (Albany NY). 2023 Oct 17;15(20):11162-11183. doi: 10.18632/aging.205119.
Ovarian cancer is one of the deadliest malignancies among females, generally having a poor prognosis. The PI3K/Akt pathway plays a vital role in the oncogenesis and progression of many types of cancer. Limited studies have fully clarified the role of PI3K/Akt pathway in the prognosis of ovarian cancer and its correlation with drug sensitivity.
A prognostic PI3K/Akt pathway related signature (PRS) was constructed with 10 machine learning algorithms using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 datasets. Gaussian mixture and logistic regression were performed to identify the optimal models for classifying lymphatic and venous invasion.
The optimal prognostic PRS developed by Lasso + survivalSVM algorithm acted as an independent risk factor for overall survival (OS) of ovarian cancer patients and had a good performance in evaluating OS rate of ovarian cancer patients. Significant correlation was obtained between PRS-based risk score and Immune score, ESTIMATE score, immune cells and cancer-related hallmarks. Low risk score indicated a lower immune escape score, TIDE score, and higher PD1&CTLA4 immunophenoscore in ovarian cancer. Moreover, PRS-based risk score acted as an indicator for drug sensitivity in the immunotherapy and chemotherapy of ovarian cancer patients.
All in all, our study developed a prognostic PRS showing powerful and good performance in predicting clinical outcome of ovarian cancer patients. PRS could serve as an indicator for drug sensitivity in the chemotherapy and immunotherapy.
卵巢癌是女性中最致命的恶性肿瘤之一,通常预后较差。PI3K/Akt 通路在多种癌症的发生和进展中起着至关重要的作用。有限的研究充分阐明了 PI3K/Akt 通路在卵巢癌预后中的作用及其与药物敏感性的相关性。
使用 TCGA、GSE14764、GSE26193、GSE26712、GSE63885 和 GSE140082 数据集,通过 10 种机器学习算法构建了一个与 PI3K/Akt 通路相关的预后特征(PRS)。使用高斯混合和逻辑回归来识别用于分类淋巴和静脉侵犯的最佳模型。
Lasso + survivalSVM 算法构建的最优预后 PRS 是卵巢癌患者总生存期(OS)的独立危险因素,在评估卵巢癌患者 OS 率方面表现良好。PRS 风险评分与免疫评分、ESTIMATE 评分、免疫细胞和癌症相关标志物之间存在显著相关性。低风险评分表明卵巢癌的免疫逃逸评分、TIDE 评分较低,PD1&CTLA4 免疫表型评分较高。此外,PRS 风险评分可作为卵巢癌患者免疫治疗和化疗药物敏感性的指标。
总之,我们的研究构建了一个预后 PRS,在预测卵巢癌患者的临床结局方面表现出强大而良好的性能。PRS 可作为卵巢癌化疗和免疫治疗药物敏感性的指标。