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Expression level of long non-coding RNA colon adenocarcinoma hypermethylated serves as a novel prognostic biomarker in patients with thyroid carcinoma.

ABSTRACT: The present study attempts to identify the prognostic value and potential mechanism of action of colorectal adenocarcinoma hypermethylated (CAHM) in thyroid carcinoma (THCA) by using the RNA sequencing (RNA-seq) dataset from The Cancer Genome Atlas (TCGA). The functional mechanism of CAHM was explored by using RNA-seq dataset and multiple functional enrichment analysis approaches. Connectivity map (CMap) online analysis tool was also used to predict CAHM targeted drugs. Survival analysis suggests that THCA patients with high CAHM expression have lower risk of death than the low CAHM expression (log-rank P=0.022, adjusted P=0.011, HR = 0.187, 95% confidence interval (CI) = 0.051-0.685). Functional enrichment of CAHM co-expression genes suggests that CAHM may play a role in the following biological processes: DNA repair, cell adhesion, DNA replication, vascular endothelial growth factor receptor, Erb-B2 receptor tyrosine kinase 2, ErbB and thyroid hormone signaling pathways. Functional enrichment of differentially expressed genes (DEGs) between low- and high-CAHM phenotype suggests that different CAHM expression levels may have the following differences in biological processes in THCA: cell adhesion, cell proliferation, extracellular signal-regulated kinase (ERK) 1 (ERK1) and ERK2 cascade, G-protein coupled receptor, chemokine and phosphatidylinositol-3-kinase-Akt signaling pathways. Connectivity map have identified five drugs (levobunolol, NU-1025, quipazine, anisomycin and sulfathiazole) for CAHM targeted therapy in THCA. Gene set enrichment analysis (GSEA) suggest that low CAHM phenotype were notably enriched in p53, nuclear factor κB, Janus kinase-signal transducer and activators of transcription, tumor necrosis factor, epidermal growth factor receptor and other signaling pathways. In the present study, we have identified that CAHM may serve as novel prognostic biomarkers for predicting overall survival (OS) in patients with THCA.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC8056003 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

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Expression level of long non-coding RNA colon adenocarcinoma hypermethylated serves as a novel prognostic biomarker in patients with thyroid carcinoma.

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