Wang Xiaojun, Ye Lei, Li Bilan
Department of Gynaecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
J Cancer. 2022 Apr 11;13(7):2213-2225. doi: 10.7150/jca.65581. eCollection 2022.
Endometrial cancer (EC) ranks fourth in the incidence rate among the most frequent gynaecological malignancies reported in the developed countries. Approximately 280,000 endometrial cancer cases are reported worldwide every year. Genomic instability and mutation are some of the favourable characteristics of human malignancies such as endometrial cancer. Studies have established that the majority of genomic mutations in human malignancies are found in the chromosomal regions that do not code for proteins. In addition, the majority of transcriptional products of these mutations are long non-coding RNAs (lncRNAs). In this study, 78 lncRNA genes were found on the basis of their mutation counts. Then, these lncRNAs were investigated to determine their relationship with genomic instability through hierarchical cluster analysis, mutation analysis, and differential analysis of driving genes responsible for genomic instability. The prognostic value of these lncRNAs was also assessed in patients with EC, and a risk factor score formula composed of 15 lncRNAs was constructed. We then identified this formula as genome instability-derived lncRNA-based gene signature (GILncSig), which stratified patients into high- and low-risk groups with significantly different outcome. And GILncSig was further validated in multiple independent patient cohorts as a prognostic factor of other clinicopathological features, such as stage, grade, overall survival rate. We observed that a high-risk score is often associated with an unfavourable prognosis in patients with EC.
子宫内膜癌（EC）在发达国家报告的最常见妇科恶性肿瘤发病率中排名第四。全球每年约报告28万例子宫内膜癌病例。基因组不稳定和突变是人类恶性肿瘤（如子宫内膜癌）的一些有利特征。研究表明，人类恶性肿瘤中的大多数基因组突变存在于不编码蛋白质的染色体区域。此外，这些突变的大多数转录产物是长链非编码RNA（lncRNA）。在本研究中，根据突变计数发现了78个lncRNA基因。然后，通过层次聚类分析、突变分析和对导致基因组不稳定的驱动基因的差异分析，对这些lncRNAs进行研究，以确定它们与基因组不稳定的关系。还评估了这些lncRNAs在EC患者中的预后价值，并构建了一个由15个lncRNAs组成的风险因素评分公式。然后，我们将这个公式确定为基于基因组不稳定衍生lncRNA的基因特征（GILncSig），它将患者分为预后明显不同的高风险组和低风险组。并且GILncSig在多个独立患者队列中作为其他临床病理特征（如分期、分级、总生存率）的预后因素得到了进一步验证。我们观察到，高风险评分通常与EC患者的不良预后相关。
