分子预后评分,高级别浆液性卵巢癌风险分层的分类器。
The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer.
发表日期:2024 Aug 02
作者:
Siddik Sarkar, Sarbar Ali Saha, Abhishek Swarnakar, Arnab Chakrabarty, Avipsa Dey, Poulomi Sarkar, Sarthak Banerjee, Pralay Mitra
来源:
Journal of Ovarian Research
摘要:
残留肿瘤、分级、国际妇产科联合会(FIGO)评分等临床病理参数常被用来预测卵巢癌患者的生存期,但高级别浆液性卵巢癌(HGSOC)的5年生存率仍然存在问题30%左右。因此,为了不懈地追求增强 HGSOC 的预后工具,本研究引入了前所未有的基于基因表达的分子预后评分 (mPS)。 mPS 通过最小绝对收缩和选择算子 (LASSO)-Cox 回归衍生自新颖的 20 基因签名,因其预测能力而脱颖而出。跨不同数据集的验证,包括训练集和测试集(每个数据集 n = 491)和大型数据集来自卵巢肿瘤组织分析 (OTTA) 联盟的 HGSOC 患者队列 (n = 7542) 一致显示,预测 5 年总生存率的曲线下面积 (AUC) 约为 0.7。 mPS 对预后的影响产生深远的影响,调整后的危险比 (HR) 为 6.1(95% CI:3.65-10.3;p< 0.001),掩盖了传统参数 - FIGO 评分、残留疾病和年龄。从 mPS 分层中收集的分子见解揭示了有趣的途径,在高风险 HGSOC 队列中,局灶粘附、Wnt 和 Notch 信号传导上调,抗原加工和呈递下调 (p<0.001)。 20-基因特征衍生的 mPS 成为临床环境中潜在的游戏规则改变者。除了预测总生存期的作用之外,其影响还延伸到指导替代疗法,特别是针对 Wnt/Notch 信号通路和免疫逃避——这是改善高危 HGSOC 患者预后的有希望的途径。© 2024。作者。
The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but the 5-year survival of high grade serous ovarian cancer (HGSOC) still remains around 30%. Hence, the relentless pursuit of enhanced prognostic tools for HGSOC, this study introduces an unprecedented gene expression-based molecular prognostic score (mPS). Derived from a novel 20-gene signature through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression, the mPS stands out for its predictive prowess.Validation across diverse datasets, including training and test sets (n = 491 each) and a large HGSOC patient cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium (n = 7542), consistently shows an area-under-curve (AUC) around 0.7 for predicting 5-year overall survival. The mPS's impact on prognosis resonates profoundly, yielding an adjusted hazard-ratio (HR) of 6.1 (95% CI: 3.65-10.3; p < 0.001), overshadowing conventional parameters-FIGO score, residual disease, and age. Molecular insights gleaned from mPS stratification uncover intriguing pathways, with focal-adhesion, Wnt, and Notch signaling upregulated, and antigen processing and presentation downregulated (p < 0.001) in high-risk HGSOC cohorts.Positioned as a robust prognostic marker, the 20-gene signature-derived mPS emerges as a potential game-changer in clinical settings. Beyond its role in predicting overall survival, its implications extend to guiding alternative therapies, especially targeting Wnt/Notch signaling pathways and immune evasion-a promising avenue for improving outcomes in high-risk HGSOC patients.© 2024. The Author(s).