Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
BMC Cancer. 2023 Aug 16;23(1):759. doi: 10.1186/s12885-023-11221-6.
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.
肺癌在全球范围内是男性和女性的主要死亡原因。越来越多的证据强调了乳酸脱氢酶 D（LDHD）在不同类型癌症中的重要性，尽管它在肺腺癌（LUAD）中的作用仍未得到充分探索。在这项研究中，我们旨在研究和确定 LDHD 与 LUAD 之间的关系。
样本的采集由癌症基因组图谱（TCGA）数据集和基因表达综合数据库（GEO）指导。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-蛋白质相互作用（PPI）网络。使用 Kaplan-Meier 方法、Cox 回归分析和列线图共同确定 LDHD 的预测值。使用 Estimate 和 ssGSEA 完成免疫浸润分析的评估。基于 TIDE 和 IPS 预测免疫治疗反应。通过 Western blot、qPCR 和免疫组织化学方法验证 LUAD 中的 LDHD 表达水平。还进行了划痕愈合和 Transwell 测定，以说明 LUAD 细胞系中的侵袭特征。
结果表明，LDHD 在 LUAD 患者中普遍下调，低 LDHD 组的 OS、DSS 和 PFI 下降。KEGG 分析显示，富集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 表达与免疫细胞浸润和典型检查点呈负相关。高 LDHD 组对免疫治疗的反应显著，尤其是在 CTAL4+ / PD1-治疗中。体外研究表明，LDHD 的过表达导致肿瘤迁移和侵袭受到抑制。
总之，我们的研究表明 LDHD 可能是预后和免疫过滤的有效预测因子，可能为免疫治疗提供更好的选择。
