DataSheet_1_Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer.pdf

BackgroundStudies have demonstrated that the regulatory role of competitive endogenous RNA (ceRNA) networks is closely related to tumorigenesis, which provides new targets for tumor therapy. In this study, the focus was to explore the ceRNA networks that regulate SLC6A8 expression and their prognosis in non-small cell lung cancer (NSCLC).
MethodsFirstly, the Cancer Genome Atlas (TCGA) data combined with immunohistochemical staining was used to compare SLC6A8 expression in NSCLC tissues and normal tissues. Thereafter, samples from the immunohistochemical staining of NSCLC were integrated with clinical follow-up data for prognostic analysis. The Starbase database was employed to search for SLC6A8-targeted miRNAs and lncRNAs, and survival analysis was performed using clinical data from TCGA to obtain SLC6A8 expression and prognosis-related ceRNA networks. Finally, the prognostic and therapeutic prospects of SLC6A8 in NSCLC were further analyzed from methylation sites and the immune microenvironment.
ResultsThe study results revealed that SLC6A8 was significantly overexpressed in NSCLC tissues compared to normal tissues, and clinical follow-up data showed that the overexpression group was associated with poor prognosis. In addition, the Starbase data combined with TCGA clinical data analysis demonstrated that the AL513318.2/hsa-miR-26a-5p/SLC6A8 network regulates SLC6A8 overexpression in NSCLC and is associated with poor prognosis. Methylation analysis revealed that 11 methylation sites were closely associated with the prognosis of NSCLC. In addition, the immune prognostic risk model showed that the high-risk group was associated with a poorer prognosis than the low-risk group, despite showing a better immunotherapy outcome.
ConclusionIn summary, the AL513318.2/hsa-miR-26a-5p/SLC6A8 network upregulates SLC6A8 expression in NSCLC and is associated with poor prognosis. Therefore it may be a prognostic biomarker of NSCLC and a potential therapeutic target.

背景
已有研究证实，竞争性内源RNA（competitive endogenous RNA, ceRNA）网络的调控作用与肿瘤发生密切相关，为肿瘤治疗提供了全新靶点。本研究旨在探索非小细胞肺癌（non-small cell lung cancer, NSCLC）中调控SLC6A8表达的ceRNA网络及其预后价值。
方法
首先，本研究结合癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据与免疫组织化学染色（immunohistochemical staining, IHC）结果，对比NSCLC组织与正常组织中SLC6A8的表达水平。随后，整合NSCLC免疫组织化学染色样本的临床随访数据进行预后分析。通过Starbase数据库检索靶向SLC6A8的微小RNA（microRNA, miRNA）及长链非编码RNA（long non-coding RNA, lncRNA），并结合TCGA临床数据开展生存分析，最终构建与SLC6A8表达及预后相关的ceRNA网络。最后，从甲基化位点与免疫微环境层面，进一步分析SLC6A8在NSCLC中的预后与治疗前景。
结果
本研究结果显示，相较于正常组织，SLC6A8在NSCLC组织中显著高表达；临床随访数据亦表明，高表达组患者预后较差。此外，结合Starbase数据与TCGA临床数据的分析结果证实，AL513318.2/hsa-miR-26a-5p/SLC6A8网络可调控NSCLC中SLC6A8的高表达，且与不良预后相关。甲基化分析发现，11个甲基化位点与NSCLC预后密切相关。同时，免疫预后风险模型结果显示，高危组患者预后较低危组更差，但免疫治疗应答更佳。
结论
综上，AL513318.2/hsa-miR-26a-5p/SLC6A8网络可上调NSCLC中SLC6A8的表达，且与不良预后相关，因此有望成为NSCLC的预后生物标志物及潜在治疗靶点。