Department of Obstetrics and Gynaecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Nursing, Huizhou First Maternal and Child Health Care Hospital, Huizhou, China.
Environ Toxicol. 2024 Mar;39(3):1650-1665. doi: 10.1002/tox.24067. Epub 2023 Nov 29.
Ovarian cancer (OV) is an aggressive malignancy that poses a significant threat to the health and lives of women. Cuproptosis is a newly discovered form of programmed cell death that offers a promising therapeutic target, although its significance in cancer progression remains uncertain. In this study, we established a prognostic model of OV with six cuproptosis-related long non-coding RNAs (lncRNAs), including CTC.246B18.8, LINC00337, RP11.568N6.1, RP11.158I9.8, RP11.678G14.3 and CYP4F26P, based on the data of The Cancer Genome Atlas (TCGA). Lower risk scores were associated with favorable prognosis. In addition, a negative outcome was associated with high expression of CTC.246B18.8. According to the ESTIMATE algorithm, CTC.246B18.8 was negatively correlated with the ImmuneScore, and positively with immune checkpoints, immune cell infiltration, and tumor mutation burden (TMB). Moreover, gene set enrichment analysis (GSEA) revealed that pathways related to immunosuppression are likely activated in response to CTC-246B18.8 overexpression. Furthermore, CTC-246B18.8 expression was also associated with the sensitivity to various chemotherapy drugs. The expression patterns of the above lncRNAs were verified in ovarian tumor cell lines (SK-OV-3, COC1, and A2780) and normal ovarian epithelial cells (IOSE - 80). Six cuproptosis-related genes (CRGs), including ATP7B, MTF1, SLC31A1, DLD, ATP7A and DLAT, were differentially expressed between CTC-246B18.8 and CTC-246B18.8 patient groups, and exhibited organ-specific expression patterns pan-cancer. Small molecule drugs that target these CRGs were predicted, and potential candidates included DIAMIDE, bathocuproine disulfonate, D-penicillamine, etc. To summarize, our findings provide molecular insights into the role of cuproptosis in OV, and the signature lncRNAs and CRGs should be investigated further as immunotherapy biomarkers of OV.
卵巢癌 (OV) 是一种侵袭性恶性肿瘤,对女性健康和生命构成重大威胁。铜死亡是一种新发现的程序性细胞死亡形式,为治疗提供了有前途的靶点,但其在癌症进展中的意义尚不确定。在这项研究中,我们基于癌症基因组图谱 (TCGA) 的数据,建立了一个由六个与铜死亡相关的长非编码 RNA (lncRNA) 组成的 OV 预后模型,包括 CTC.246B18.8、LINC00337、RP11.568N6.1、RP11.158I9.8、RP11.678G14.3 和 CYP4F26P。较低的风险评分与良好的预后相关。此外,高表达 CTC.246B18.8 与不良预后相关。根据 ESTIMATE 算法,CTC.246B18.8 与免疫评分呈负相关,与免疫检查点、免疫细胞浸润和肿瘤突变负荷 (TMB) 呈正相关。此外,基因集富集分析 (GSEA) 显示,CTC-246B18.8 过表达可能激活与免疫抑制相关的途径。此外,CTC-246B18.8 的表达与各种化疗药物的敏感性也有关。在卵巢肿瘤细胞系 (SK-OV-3、COC1 和 A2780) 和正常卵巢上皮细胞 (IOSE-80) 中验证了上述 lncRNA 的表达模式。六个与铜死亡相关的基因 (CRGs),包括 ATP7B、MTF1、SLC31A1、DLD、ATP7A 和 DLAT,在 CTC-246B18.8 和 CTC-246B18.8 患者组之间表达差异,在泛癌中表现出器官特异性表达模式。预测了针对这些 CRGs 的小分子药物,潜在的候选药物包括 DIAMIDE、bathocuproine disulfonate、D-penicillamine 等。总之,我们的研究结果为铜死亡在 OV 中的作用提供了分子见解,并且该特征 lncRNA 和 CRGs 应作为 OV 的免疫治疗生物标志物进一步研究。