肺癌被报道为男性和女性全球范围内的主要死因。越来越多的证据突出了乳酸脱氢酶D（LDHD）在不同类型的癌症中的重要性，尽管其在肺腺癌（LUAD）中的作用尚未充分探索。在本研究中，我们旨在调查和确定LDHD与LUAD之间的关系。样本的收集是根据癌症基因组图谱（TCGA）数据集和基因表达数据库（GEO）进行的。为了确定LDHD功能的各个方面，我们分析了不同的表达基因（DEGs）、功能富集和蛋白质相互作用（PPI）网络。使用Kaplan-Meier方法、Cox回归分析和诺莫图共同确定了LDHD的预测值。采用Estimate和ssGSEA评估了免疫浸润分析。免疫疗法反应的预测基于TIDE和IPS。通过免疫组织化学、Western blot和qPCR方法验证了LUAD中LDHD的表达水平。还进行了划痕愈合和透过培养皿示踪试验，以说明LUAD细胞系中的侵袭特征。结果显示，在LUAD患者中，LDHD普遍下调，低LDHD组的整体生存(OS)、疾病特异生存(DSS)和进展无病生存(PFI)相对下降。通过KEGG分析观察到富集的途径包括丙酮酸代谢、中心碳代谢和氧化磷酸化。还注意到LDHD的表达与免疫细胞浸润和典型检查点呈负相关。高LDHD组对免疫疗法的反应显著，尤其在CTLA4+/PD1-疗法中。体外研究表明，LDHD的过表达抑制了肿瘤的迁移和侵袭。总之，我们的研究揭示了LDHD可能是预后和免疫浸润的有效预测因子，可能为免疫疗法提供更好的选择。© 2023. 由 Springer Nature 旗下的 BioMed Central Ltd. 提供。

Lung cancer is reported to be the leading cause of death in males and females, globally. Increasing evidence highlights the paramount importance of Lactate dehydrogenase D (LDHD) in different types of cancers, though it's role in lung adenocarcinoma (LUAD) is still inadequately explored. In this study, we aimed to investigate and determine the relationship between LDHD and LUAD.The collection of the samples was guided by The Cancer Genome Atlas (TCGA) datasets and Gene Expression Omnibus (GEO). To ascertain various aspects around LDHD function, we analyzed different expression genes (DEGs), functional enrichment, and protein-protein interaction (PPI) networks. The predictive values for LDHD were collectively determined using the Kaplan-Meier method, Cox regression analysis, and a nomogram. Evaluation of the immune infiltration analysis was completed using Estimate and ssGSEA. The prediction of the immunotherapy response was based on TIDE and IPS. The LDHD expression levels in LUAD were validated through Western blot, qPCR, and immunohistochemistry methods. Wound healing and transwell assays were also performed to illustrate the aggressive features in LUAD cell lines.The results showed that LDHD was generally downregulated in LUAD patients, with the low LDHD group presenting a decline in OS, DSS, and PFI. Enriched pathways, which include pyruvate metabolism, central carbon metabolism, and oxidative phosphorylation were observed through KEGG analysis. It was also noted that the expression of LDHD expression was inversely related to immune cell infiltration and typical checkpoints. The high LDHD group's response to immunotherapy was remarkable, particularly in CTAL4 + /PD1- therapy. In vitro studies revealed that the overexpression of LDHD caused tumor migration and invasion to be suppressed.In conclusion, our study revealed that LDHD might be an effective predictor of prognosis and immune filtration, possibly leading to better choices for immunotherapy.© 2023. BioMed Central Ltd., part of Springer Nature.