DataSheet1_Comprehensive analysis of the cuproptosis-related gene DLD across cancers: A potential prognostic and immunotherapeutic target.zip

DLD is a key gene involved in “cuproptosis,” but its roles in tumor progression and immunity remain unclear. Exploring the potential mechanisms and biological roles of DLD may provide new insights for therapeutic strategies for tumors. In the present study, we analyzed the role of DLD in a variety of tumors by using several bioinformatic tools. The results showed that compared with normal tissues, tumor tissues representing multiple cancers showed significant differential expression of DLD. High DLD expression was associated with a good prognosis in BRCA, KICH, and LUAD. Conversely, high expression levels of DLD were detrimental to patient prognosis in many other tumors, such as COAD, KIRC, and KIRP. In addition, the associations of DLD with infiltrating immune cells, genetic alterations and methylation levels across cancers were assessed. Aberrant expression of DLD was positively correlated with most infiltrating immune cells, especially neutrophils. The DLD methylation level was significantly decreased in COAD, LIHC, and LUSC but significantly increased in BRCA. DLD had the highest mutation rate (6.04%) in ESCA. In LUSC, patients with genetic alterations in DLD showed a poorer prognosis. At the single-cell level, the roles of DLD in regulating cancer-associated biological functions, such as metastasis, inflammation, and differentiation, were explored. Afterward, we further investigated whether several disease-associated genes could be correlated with DLD. GO enrichment analysis indicated that DLD-related genes were mainly associated with mitochondria-related cellular components, aerobic respiration and the tricarboxylic acid cycle. Finally, the correlations between DLD expression and immunomodulatory genes, immune checkpoints, and sensitivity to some antitumor drugs were investigated. It is worth noting that DLD expression was positively correlated with immune checkpoint genes and immunomodulatory genes in most cancers. In conclusion, this study comprehensively analyzed the differential expression, prognostic value and immune cell infiltration-related function of DLD across cancers. Our results suggest that DLD has great potential to serve as a candidate marker for pancancer prognosis and immunotherapy and may provide a new direction for cancer treatment development.

二氢硫辛酰胺脱氢酶（DLD）是参与铜死亡（Cuproptosis）的关键基因，但其在肿瘤进展与免疫调控中的作用仍不明确。探索DLD的潜在作用机制及生物学功能，可为肿瘤治疗策略提供全新研究视角。本研究借助多款生物信息学工具，系统分析了DLD在多种肿瘤中的表达与功能。结果显示，相较于正常组织，多种癌症的肿瘤组织中DLD的表达水平存在显著差异。在乳腺浸润癌（BRCA）、肾嫌色细胞癌（KICH）与肺腺癌（LUAD）中，高表达DLD与患者良好预后显著相关；反之，在结肠腺癌（COAD）、肾透明细胞癌（KIRC）及肾乳头状细胞癌（KIRP）等多数其他肿瘤中，高表达DLD则会恶化患者预后结局。此外，本研究还评估了DLD与泛癌队列中浸润免疫细胞、遗传变异及甲基化水平的关联。DLD的异常表达与多数浸润免疫细胞呈正相关，尤以中性粒细胞最为显著。在结肠腺癌（COAD）、肝细胞癌（LIHC）与肺鳞状细胞癌（LUSC）中，DLD的甲基化水平显著降低；而在乳腺浸润癌（BRCA）中则显著升高。DLD在食管腺癌（ESCA）中的突变率最高，达6.04%。在肺鳞状细胞癌（LUSC）中，携带DLD遗传变异的患者预后更差。在单细胞转录组层面，本研究探究了DLD在调控肿瘤相关生物学功能（如肿瘤转移、炎症反应与细胞分化）中的作用。随后，本研究进一步分析了多种疾病相关基因与DLD的表达相关性。基因本体（GO）富集分析结果表明，DLD相关基因主要富集于线粒体相关细胞组分、有氧呼吸通路及三羧酸循环过程。最后，本研究探讨了DLD表达与免疫调节基因、免疫检查点及部分抗肿瘤药物敏感性的关联。值得注意的是，在多数癌症中，DLD的表达与免疫检查点基因及免疫调节基因呈显著正相关。综上，本研究全面分析了DLD在泛癌中的差异表达特征、预后价值及与免疫细胞浸润相关的功能。我们的研究结果提示，DLD有望成为泛癌预后评估与免疫治疗的候选标志物，可为癌症治疗的研发提供新的方向。