Gu Jiahui, Wang Zihao, Wang B O, Ma Xiaoxin
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Front Oncol. 2023 Mar 3;13:1097015. doi: 10.3389/fonc.2023.1097015. eCollection 2023.
Endometrial cancer (EC) is a common gynecological cancer worldwide and the sixth most common female malignant tumor. A large number of studies conducted through database mining have identified many biomarkers that may be related to survival and prognosis. However, the predictive ability of single-gene biomarkers is not sufficiently accurate. In recent years, tumors have been shown to interact closely with their microenvironment, and tumor-infiltrating immune cells in the tumor microenvironment were associated with therapeutic effects. Furthermore, sequencing technology has evolved and allowed the identification of genetic signatures that may improve prediction results. The purpose of this research was to discover the Cancer Genome Atlas (TCGA) data to evaluate new genetic features that can predict the prognosis of EC.
mRNA expression profiling was analyzed in patients with EC identified in the TCGA database (n = 530). Differentially expressed genes at different stages of EC were screened using the immune cell enrichment score (ImmuneScore). Univariate and multivariate Cox regression analyses was applied to evaluate genes significantly related to overall survival and establish the prognostic risk parameter formula. Kaplan-Meier survival curves and the logarithmic rank method were applied to verify the importance of risk parameters for the prognostic forecast. The accuracy of survival prediction was confirmed using the nomogram and Receiver Operating Characteristic (ROC) curve analysis. The mRNA expression of eight genes were measured by qRT-PCR. According to COX and HR values, NBAT1, a representative gene among 8 genes, was selected for CCK-8 assay, colony formation assay and transwell invasion assay to verify the effect on survival.
Eight related genes (, , , , , , , and ) were discovered to be significantly associated with the overall survival rate. According to these eight-gene signatures, 530 patients with EC were assigned to high- and low-risk subgroups. The prognostic capability of the eight-gene signature was not influenced by other elements.
Eight related gene markers were identified using ImmuneScore, which could predict prognosis and survival in patients with EC. These findings provide a basis for understanding the application of biological information in tumors and identifying the poor prognosis of EC.
子宫内膜癌(EC)是全球常见的妇科癌症,也是女性第六大常见恶性肿瘤。通过数据库挖掘进行的大量研究已经确定了许多可能与生存和预后相关的生物标志物。然而,单基因生物标志物的预测能力不够准确。近年来,肿瘤已被证明与其微环境密切相互作用,肿瘤微环境中的肿瘤浸润免疫细胞与治疗效果相关。此外,测序技术不断发展,使得能够识别可能改善预测结果的基因特征。本研究的目的是挖掘癌症基因组图谱(TCGA)数据,以评估可预测EC预后的新基因特征。
对TCGA数据库中确诊的EC患者(n = 530)进行mRNA表达谱分析。使用免疫细胞富集评分(ImmuneScore)筛选EC不同阶段的差异表达基因。应用单变量和多变量Cox回归分析评估与总生存显著相关的基因,并建立预后风险参数公式。采用Kaplan-Meier生存曲线和对数秩检验方法验证风险参数对预后预测的重要性。使用列线图和受试者工作特征(ROC)曲线分析确认生存预测的准确性。通过qRT-PCR检测8个基因的mRNA表达。根据COX和HR值,从8个基因中选择代表性基因NBAT1进行CCK-8实验、集落形成实验和Transwell侵袭实验,以验证其对生存的影响。
发现8个相关基因(,,,,,,,和)与总生存率显著相关。根据这8个基因特征,将530例EC患者分为高风险和低风险亚组。8基因特征的预后能力不受其他因素影响。
利用ImmuneScore鉴定出8个相关基因标志物,可预测EC患者的预后和生存。这些发现为理解生物信息在肿瘤中的应用及识别EC预后不良提供了依据。