Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China.
The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
World J Surg Oncol. 2023 Oct 21;21(1):332. doi: 10.1186/s12957-023-03229-w.
To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics.
EC patients who underwent surgery between June 2018 and June 2022 at Peking University People's Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed.
(1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P < 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P < 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444-1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010).
In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC.
根据临床病理特征对低拷贝数（CNL）子宫内膜癌（EC）患者进行分层。
纳入 2018 年 6 月至 2022 年 6 月期间在北京大学人民医院接受手术的 EC 患者，并根据 TCGA 分子分型进一步分类：POLE 超突变型、微卫星不稳定高（MSI-H）型、CNL 型和拷贝数高（CNH）型。回顾性分析 CNL 患者的临床病理特征和预后。应用 Cox 比例风险回归模型进行单因素和多因素分析，确定独立的危险因素。根据 TCGA 项目中 CNL 病例的转录组筛选总生存期（OS）相关的差异表达基因（DEGs）。最后，建立列线图，并进行准确性分析。
（1）共纳入 279 例 EC 患者，其中 168 例（60.2%）为 CNL 组。21 例患者复发，6 例患者死亡，4 种分子亚型之间无显著差异（P=0.104），但 OS 有统计学意义（P=0.036）。（2）CNL 患者分为复发组和非复发组，两组在病理类型、FIGO 分期、ER、PR、糖化血红蛋白（HbA1c）和高密度脂蛋白胆固醇（HDL-C）方面存在显著差异（P<0.05）。所有上述因素均纳入单因素和多因素 Cox 回归模型，其中病理类型、PR 和 HDL-C 有统计学差异（P<0.05），是 CNL 组患者预后的三个独立危险因素。（3）通过比较 TCGA 数据库中存活和死亡的 CNL 患者肿瘤组织的转录组，筛选出 903 个（4.4%）差异表达基因，其中四个脂质代谢途径显著富集。最后，建立了一个列线图，并进行了内部交叉验证，AUC 为 0.831，C 指数为 0.748（95%CI 0.444-1.052），具有良好的区分准确性。（4）根据建立的列线图和中位数总评分（85.89），患者分为高评分组（n=85）和低评分组（n=83），8 例复发患者均在高评分组。两组间进行生存分析，RFS 差异有统计学意义（P=0.010）。
在 CNL 型 EC 患者中，病理类型、PR 和 HDL-C 是独立的预后危险因素，基于此建立的列线图对 CNL EC 患者的复发风险具有良好的预测能力。
