Chen Yun
Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Front Genet. 2022 Jul 22;13:912037. doi: 10.3389/fgene.2022.912037. eCollection 2022.
Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy globally with high recurrence and mortality rates. Cuproptosis is a new type of programmed cell death involved in tumor cell proliferation and growth, angiogenesis, and metastasis. The difference in cuproptosis-related genes (CRGs) between UCEC tissues and normal tissues deposited in The Cancer Genome Atlas database was calculated using the "limma" R package. LASSO Cox regression analysis was conducted to construct a prognostic cuproptosis-related signature. Kaplan-Meier analysis was conducted to compare the survival of UCEC patients. A ceRNA network was constructed to identify the lncRNA-miRNA-mRNA regulatory axis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to verify CRG expression in UCEC. The expression of FDX1, LIAS, DLAT, and CDKN2A were upregulated, whereas the expression of LIPT1, DLD, PDHB, MTF1, and GLS were downregulated in UCEC versus normal tissues. The genetic mutation landscape of CRGs in UCEC was also summarized. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these CRGs were enriched in the tricarboxylic acid (TCA) cycle, glycolysis, and HIF-1 signaling pathway. LASSO Cox regression analysis was performed and identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1). UCEC patients with high risk scores had a poor prognosis with an area under the curve of 0.782 and 0.764 on 3- and 5-year receiver operating characteristic curves. Further analysis demonstrated a significant correlation between CDKN2A and pTNM stage, tumor grade, immune cell infiltration, drug sensitivity, tumor mutational burden (TMB) score, and microsatellite instable (MSI) score. The data validation of qRT-PCR further demonstrated the upregulation of CDKN2A and the downregulation of LIPT1 and GLS in UCEC versus normal tissues. The ceRNA network also identified lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis for UCEC. The current study identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1) for UCEC. The ceRNA network also identified that lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis may be involved in the progression of UCEC. Further and studies should be conducted to verify these results.
子宫体子宫内膜癌（UCEC）是全球常见的妇科恶性肿瘤，复发率和死亡率很高。铜死亡是一种新型的程序性细胞死亡，与肿瘤细胞的增殖、生长、血管生成和转移有关。使用“limma”R包计算了癌症基因组图谱数据库中UCEC组织和正常组织之间铜死亡相关基因（CRG）的差异。进行LASSO Cox回归分析以构建与铜死亡相关的预后特征。进行Kaplan-Meier分析以比较UCEC患者的生存率。构建ceRNA网络以识别lncRNA-miRNA-mRNA调控轴。进行定量逆转录-聚合酶链反应（qRT-PCR）以验证UCEC中CRG的表达。与正常组织相比，UCEC中FDX1、LIAS、DLAT和CDKN2A的表达上调，而LIPT1、DLD、PDHB、MTF1和GLS的表达下调。还总结了UCEC中CRG的基因突变图谱。基因本体论和京都基因与基因组百科全书分析表明，这些CRG在三羧酸（TCA）循环、糖酵解和HIF-1信号通路中富集。进行LASSO Cox回归分析并确定了一个与铜死亡相关的预后特征，包括这三个预后生物标志物（CDKN2A、GLS和LIPT1）。高风险评分的UCEC患者预后较差，在3年和5年的受试者工作特征曲线上的曲线下面积分别为0.782和0.764。进一步分析表明，CDKN2A与pTNM分期、肿瘤分级、免疫细胞浸润、药物敏感性、肿瘤突变负荷（TMB）评分和微卫星不稳定（MSI）评分之间存在显著相关性。qRT-PCR的数据验证进一步证明，与正常组织相比，UCEC中CDKN2A上调，LIPT1和GLS下调。ceRNA网络还确定了UCEC的lncRNA XIST/miR-125a-5p/CDKN2A调控轴。当前研究确定了一个与铜死亡相关的预后特征，包括UCEC的这三个预后生物标志物（CDKN2A、GLS和LIPT1）。ceRNA网络还确定lncRNA XIST/miR-1
