Zheng Qiuqing, Xie Yingjun, Xu Luyin, Chen Delian, Wu Jianfeng, Liu Shuxun, Wu Lili, Fang Peiwei, Xie Fajun
Department of Ultrasound, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
J Gastrointest Oncol. 2024 Aug 31;15(4):1746-1759. doi: 10.21037/jgo-24-560. Epub 2024 Aug 28.
Lactate dehydrogenase A () plays a crucial role in the final step of anaerobic glycolysis, converting L-lactate and NAD to pyruvate and nicotinamide adenine dinucleotide (NADH). Its high expression has been linked to tumorigenesis and patient survival in various human cancers. However, the full implications of 's role and its correlation with clinicopathological features in pancreatic adenocarcinoma (PAAD) remain to be fully understood. This study was thus conducted to elucidate the specific functions of in PAAD, with the aim of providing more robust evidence for clinical diagnosis and treatment.
In an extensive systems analysis, we searched through numerous databases, including The Cancer Genome Atlas (TCGA) and Oncomine. Our objective was to clarify the clinical implications and functional role of in PAAD. Bioinformatics was used to identify the biological function of expression and its correlation with tumor immune status.
Our analysis revealed that the gene is overexpressed in PAAD and that this upregulation was associated with a worse patient prognosis. Through gene set enrichment analysis, we found that 's influence on PAAD is linked to signaling pathways involving Kirsten rat sarcoma viral oncogene homolog (), transforming growth factor-β (), and hypoxia inducible factor-1 (). Mutation of could upregulate its own expression and was positively correlated with expression. Moreover, our data demonstrated that expression was linked to immune infiltration and poor prognosis in PAAD, indicating its role in disease pathogenesis. Overexpression of may suppress tumor immunity, suggesting it as a potential target for the diagnosis and treatment of PAAD, thus providing new insights into managing this aggressive cancer.
Overall, our results showed that as a prognostic biomarker could serve as a novel target for future PAAD immunotherapy.
乳酸脱氢酶A（LDHA）在无氧糖酵解的最后一步中起着关键作用，将L-乳酸和NAD转化为丙酮酸和烟酰胺腺嘌呤二核苷酸（NADH）。其高表达与多种人类癌症的肿瘤发生和患者生存相关。然而，LDHA在胰腺腺癌（PAAD）中的作用及其与临床病理特征的相关性仍有待充分了解。因此，本研究旨在阐明LDHA在PAAD中的具体功能，为临床诊断和治疗提供更有力的证据。
在广泛的系统分析中，我们搜索了众多数据库，包括癌症基因组图谱（TCGA）和Oncomine。我们的目标是阐明LDHA在PAAD中的临床意义和功能作用。利用生物信息学确定LDHA表达的生物学功能及其与肿瘤免疫状态的相关性。
我们的分析显示，LDHA基因在PAAD中过表达，这种上调与患者预后较差有关。通过基因集富集分析，我们发现LDHA对PAAD的影响与涉及 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）、转化生长因子-β（TGF-β）和缺氧诱导因子-1（HIF-1）的信号通路有关。LDHA的突变可上调其自身表达，并与KRAS表达呈正相关。此外，我们的数据表明，LDHA表达与PAAD中的免疫浸润和预后不良有关，表明其在疾病发病机制中的作用。LDHA的过表达可能会抑制肿瘤免疫，提示其作为PAAD诊断和治疗的潜在靶点，从而为管理这种侵袭性癌症提供新的见解。
总体而言，我们的结果表明，LDHA作为一种预后生物标志物可作为未来PAAD免疫治疗的新靶点。
