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Construction and validation of a prognostic model based on 11 lymph node metastasis‐related genes for overall survival in endometrial cancer

列线图 比例危险模型 肿瘤科 医学 子宫内膜癌 一致性 内科学 淋巴结 阶段(地层学) Lasso(编程语言) 转移 接收机工作特性 危险系数 生存分析 癌症 生物 置信区间 万维网 古生物学 计算机科学
作者
Hong Wu,Haiqin Feng,Xiaowei Miao,Jiancai Ma,Cairu Liu,Lina Zhang,Liping Yang
出处
期刊:Cancer Medicine [Wiley]
卷期号:11 (23): 4641-4655 被引量:4
标识
DOI:10.1002/cam4.4844
摘要

Endometrial cancer (EC) is one of the most common malignant tumors in female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic models and effective biomarkers for early diagnosis is important to reduce the mortality rate.A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish porgnostic LNM related genes signature. Subsequently, a novel prognosis-related nomogram was constructed to predict overall survival (OS). Survival analysis was carried out to explore the individual prognostic significance of the risk model and key gene was validated in vitro.In total, 89 lymph node related genes (LRGs) were identified. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better OS (p = 3.583e-08). The area under the ROC curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival verification performed in three subgroups from the nomogram demonstrated the validity of the model. The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. External validation with 30 patients in our hospital showed that patients with low-risk scores had a longer OS (p-value = 0.03). Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively.Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients.
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