Abstract

BackgroundThe occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.MethodsThe expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.ResultsExpression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.ConclusionsLINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.

Highlights

  • According to Global Cancer Statistics 2020, with an estimated 2.2 million new cancer cases and 1.8 million deaths, lung cancer was the second most commonly diagnosed cancer and the leading cause of cancer death in 2020, representing approximately one in 10 (11.4%) cancers diagnosed and one in 5 (18.0%) deaths [1,2,3,4]

  • The GSE40791 and GSE33532 datasets showed that the expression of LINC00973

  • In the GEPIA database, we found that the expression levels of RTKN2, NFIX, PTX3 and BMP2 in non-small cell carcinoma (NSCLC) subtypes LUAD and LUSC tissues were significantly declined, while the expression of LOXL2 in NSCLC tissues increased (Figure S3)

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Summary

Introduction

According to Global Cancer Statistics 2020, with an estimated 2.2 million new cancer cases and 1.8 million deaths, lung cancer was the second most commonly diagnosed cancer and the leading cause of cancer death in 2020, representing approximately one in 10 (11.4%) cancers diagnosed and one in 5 (18.0%) deaths [1,2,3,4]. With the improvement of treatment methods, the prognosis of cancer patients was improved, but the overall survival (OS) of NSCLC patients remained still frustrating. LCAT1, a member of long non-coding RNA (lncRNA), was an upregulated marker in lung cancer tissues. Elevated LCAT1 expression level was closely associated with poor prognosis of cancer patients [6]. LncRNA MNX1-AS1 was upregulated in lung cancer tissues, and the prognosis of lung cancer patients with overexpression of MNX1-AS1 was often terrible. The expression of LncRNA AFAP1-AS1 was increased in NSCLC tissues, and related to the TNM stage and tumor size of NSCLC patients. The occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis

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