Institute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.
Histol Histopathol. 2024 Jul;39(7):867-876. doi: 10.14670/HH-18-731. Epub 2024 Mar 7.
Lung cancer is a major cause of cancer-related death worldwide and effective therapies, besides surgery, are available only for a small proportion of patients. Since cellular respiration is known to be broadly altered in malignant tumors, the cellular processes of respiration can be a potential therapeutic target. One important element of cellular respiration is creatine and its transport by the creatine transporter SLC6A8. Here we describe the expression of SLC6A8 at the RNA and protein level, epigenetic modifications as well as survival analysis in NSCLC tissues and matched controls.
We analyzed epigenetic modifications of the gene in 32 patients, of which 18 were additionally analyzed by transcriptome analysis. The expression of SLC6A8 at the protein level was assessed by immunohistochemistry using an independent cohort and correlated with clinicopathological data including survival. Kaplan-Meier analysis was performed to analyze the possible effects of the transcriptional levels of in another separate cohort (n=1925).
loci are epigenetically modified in NSCLC compared with tumor-free controls. SLC6A8 is upregulated in NSCLC at the RNA and protein level. High mRNA expression of was associated with an overall poor prognosis in lung adenocarcinoma patients and displayed the strongest adverse prognostic effect in male smokers with adenocarcinomas. Results of transcriptome analysis were partially confirmed at the protein level.
Our results suggest an important role of creatine and its transport via SLC6A8 in NSCLC.
肺癌是全球癌症相关死亡的主要原因，除了手术之外，有效的治疗方法仅适用于一小部分患者。由于已知恶性肿瘤中细胞呼吸广泛改变，因此细胞呼吸过程可能是潜在的治疗靶点。细胞呼吸的一个重要元素是肌酸及其由肌酸转运蛋白 SLC6A8 转运。在这里，我们描述了 SLC6A8 在非小细胞肺癌组织和匹配对照中的 RNA 和蛋白质水平的表达、表观遗传修饰以及生存分析。
我们分析了 32 名患者中 基因的表观遗传修饰，其中 18 名患者还通过转录组分析进行了分析。使用独立队列通过免疫组织化学评估 SLC6A8 在蛋白质水平的表达，并与包括生存在内的临床病理数据相关联。Kaplan-Meier 分析用于分析另一个独立队列（n=1925）中 的转录水平的可能影响。
与无肿瘤对照相比， 基因在非小细胞肺癌中存在表观遗传修饰。SLC6A8 在非小细胞肺癌中在 RNA 和蛋白质水平上均上调。高 表达与肺腺癌患者的总体预后不良相关，并且在患有腺癌的男性吸烟者中显示出最强的不利预后影响。蛋白质水平的转录组分析结果部分得到证实。
我们的结果表明肌酸及其通过 SLC6A8 在非小细胞肺癌中的转运具有重要作用。
