Li Chunwei, Zhu Lili, Liu Qinghua, Peng Mengle, Deng Jinhai, Fan Zhirui, Duan Xiaoran, Xue Ruyue, Guo Zhiping, Lv Xuefeng, Li Lifeng, Zhao Jie
National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Heliyon. 2024 Jul 2;10(14):e34011. doi: 10.1016/j.heliyon.2024.e34011. eCollection 2024 Jul 30.
Cancer is widely regarded as a leading cause of death in humans, with colon adenocarcinoma (COAD) ranking among the most prevalent types. Cuproptosis is a novel form of cell death mediated by protein lipoylation. Cuproptosis-related genes (CRGs) participate in tumourigenesis and development. Their role in pan-cancer and COAD require further investigation. This study comprehensively evaluated the relationship among CRGs, pan-cancer, and COAD. Our research revealed the differential expression of CRGs and the cuproptosis potential index (CPI) between normal and tumour tissues, and further explored the correlation of CRGs or CPI with prognosis, immune infiltration, tumor mutant burden(TMB), microsatellite instability (MSI), and drug sensitivity in pan-cancer. Gene set enrichment analysis (GSEA) revealed that oxidative phosphorylation and fatty acid metabolism pathways were significantly enriched in the high CPI group of most tumours. FDX1 and CDKN2A were chosen for further exploration, and we found an independent association between FDX1 and CDKN2A and prognosis, immune infiltration, TMB, and MSI in pan-cancer. Furthermore, a prognostic risk model based on the association between CRGs and COAD was built, and the correlations between the risk score and prognosis, immune-related characteristics, and drug sensitivity were analysed. COAD was then divided into three subtypes using cluster analysis, and the differences among the subtypes in prognosis, CPI, immune-related characteristics, and drug sensitivity were determined. Due to the level of LIPT1 was notably positive related with the risk score, the cytological identification was carried out to identify the association of LIPT1 with proliferation and migration of colon cancer cells. In summary, CRGs can be used as potential prognostic biomarkers to predict immune infiltration levels in patients with pan-cancer. In addition, the risk model could more accurately predict the prognosis and immune infiltration levels of COAD and better guide the direction of clinical medication. Thus, FDX1, CDKN2A, and LIPT1 may serve as prospective new targets for cancer therapy.
癌症被广泛认为是人类的主要死因，其中结肠腺癌（COAD）是最常见的类型之一。铜死亡是一种由蛋白质脂酰化介导的新型细胞死亡形式。铜死亡相关基因（CRGs）参与肿瘤的发生和发展。它们在泛癌和COAD中的作用需要进一步研究。本研究全面评估了CRGs、泛癌和COAD之间的关系。我们的研究揭示了正常组织和肿瘤组织之间CRGs的差异表达以及铜死亡潜能指数（CPI），并进一步探讨了CRGs或CPI与泛癌预后、免疫浸润、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和药物敏感性的相关性。基因集富集分析（GSEA）显示，氧化磷酸化和脂肪酸代谢途径在大多数肿瘤的高CPI组中显著富集。选择FDX1和CDKN2A进行进一步探索，我们发现FDX1和CDKN2A与泛癌预后、免疫浸润、TMB和MSI之间存在独立关联。此外，建立了基于CRGs与COAD关联的预后风险模型，并分析了风险评分与预后、免疫相关特征和药物敏感性之间的相关性。然后使用聚类分析将COAD分为三个亚型，并确定各亚型在预后、CPI、免疫相关特征和药物敏感性方面的差异。由于LIPT1水平与风险评分显著正相关，因此进行了细胞学鉴定以确定LIPT1与结肠癌细胞增殖和迁移的关联。总之，CRGs可作为潜在的预后生物标志物来预测泛癌患者的免疫浸润水平。此外，该风险模型可以更准确地预测COAD的预后和免疫浸润水平，并更好地指导临床用药方向。因此，FDX1、CDKN2A和LIPT1可能成为癌症治疗的潜在新靶点。
