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基于戊糖磷酸代谢途径相关长非编码 RNA 鉴定肺腺癌的两种亚型和预后特征。

Identification of Two Subtypes and Prognostic Characteristics of Lung Adenocarcinoma Based on Pentose Phosphate Metabolic Pathway-Related Long Non-coding RNAs.

机构信息

Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Front Public Health. 2022 Jun 21;10:902445. doi: 10.3389/fpubh.2022.902445. eCollection 2022.

Abstract

This study analyzed the differences in subtypes and characteristics of advanced lung adenocarcinoma (LUAD) patients based on the pentose phosphate metabolic pathway-related long non-coding RNAs (lncRNAs), along with their potential regulatory mechanisms. Using the expression profiling and corresponding clinical information of LUAD patients from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Differential pathway scores between normal and tumor samples from TCGA were identified by rank-sum tests. Pearson correlation coefficients between pentose phosphate scores of the pentose phosphate samples and lncRNAs of the corresponding datasets were calculated. Next, the clusterProfiler software package was used for functional annotation. Clustering of pentose phosphate-related lncRNAs from LUAD samples categorized two molecular subtypes (C1, and C2). C1 was associated with a lower pentose phosphate score and a good prognosis; the C2 showed a higher pentose phosphate score and was related to poorer prognoses. The C2 was markedly associated with energy metabolic pathways. The expression of most immune cells were markedly higher in C1 subtype. Some crucial immune checkpoints, including CTLA4, CD274, and CD47, were also significantly upregulated in C1 subtype, leading to a higher score of clinical effect on the C1 subtype. Finally, one TF, BACH1, was found to be significantly upregulated in C1 subtypes; the pathways activated by this TF may be associated with tumor progression and poor prognoses. LUAD typing based on pentose phosphate metabolic pathway-related lncRNAs was confirmed. Differences in characteristics between C1 and C2 subtypes improved the current LUAD detection and treatment.

摘要

本研究基于戊糖磷酸代谢途径相关长链非编码 RNA(lncRNA)分析了晚期肺腺癌(LUAD)患者的亚型和特征差异及其潜在的调控机制。使用基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)中 LUAD 患者的表达谱和相应的临床信息。通过秩和检验鉴定 TCGA 中正常和肿瘤样本之间的差异途径分数。计算戊糖磷酸分数与相应数据集 lncRNA 之间的 Pearson 相关系数。接下来,使用 clusterProfiler 软件包进行功能注释。从 LUAD 样本中聚类的戊糖磷酸相关 lncRNA 分为两个分子亚型(C1 和 C2)。C1 与较低的戊糖磷酸分数和较好的预后相关;C2 显示出较高的戊糖磷酸分数,与较差的预后相关。C2 与能量代谢途径明显相关。C1 亚型中大多数免疫细胞的表达明显升高。C1 亚型中一些关键的免疫检查点,包括 CTLA4、CD274 和 CD47,也明显上调,导致 C1 亚型的临床效果评分更高。最后,发现一个 TF,BACH1,在 C1 亚型中显著上调;该 TF 激活的途径可能与肿瘤进展和不良预后有关。基于戊糖磷酸代谢途径相关 lncRNA 的 LUAD 分型得到了证实。C1 和 C2 亚型之间特征的差异改善了当前的 LUAD 检测和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/356e/9253426/63be9f0815a2/fpubh-10-902445-g0001.jpg

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