Potential Prognostic Biomarkers of Lung Adenocarcinoma Based on Bioinformatic Analysis

Abstract

Lung adenocarcinoma (LUAD), which accounts for 60% of non-small-cell lung cancers, is poorly diagnosed and has a low average 5-year survival rate (approximately 20%). It remains the leading cause of cancer-related deaths worldwide. Studies on long noncoding RNAs (lncRNAs) in LUAD-related competing endogenous RNA (ceRNA) networks are limited. We aimed to identify novel prognostic biomarkers for LUAD using bioinformatic tools and data analysis. We systemically integrated differentially expressed genes and clinically significant modules using weighted correlation network analysis. We performed a functional analysis of the collected candidate genes and explored three LUAD-related genes (VWF, PECAM1, and COL1A1) associated with the overall survival rates of patients with LUAD. Based on Cox proportional hazards analysis of candidate mRNAs and lncRNAs together with differentially expressed microRNAs, we constructed ceRNA networks, obtained 12 lncRNAs in the ceRNA networks, and revealed seven novel lncRNAs AC021016.2, AC079630.1, AC116407.1, AC125807.2, AF131215.5, LINC01936, and RHOXF1-AS1. These lncRNAs were found to be associated with overall survival rates and are suitable for the prediction of prognosis by Kaplan-Meier survival and receiver operating characteristic curve analyses. In particular, three lncRNAs—AF131215.5, AC125807.2, and LINC01936—showed an independent prognostic value of overall survival for patients with LUAD. We evaluated the diagnostic capabilities of seven lncRNAs for patients with LUAD using principal component analysis and the Gene Set Variation Analysis index. lncRNAs and crucial genes could be effectively used for distinguishing LUAD tumors from normal tissues in the Gene Expression Omnibus profile. In particular, AC021016.2 showed a significant prognostic value in the validation dataset. Our findings reveal the significance of exploring lncRNAs in cancer-related ceRNAs using bioinformatic strategies.

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

“…The results in Supplementary Figure S3 showed that FMR1-IT1 and PTOV1-AS2 can be detected in clinical diagnosis. AF131215.5 is one of lncRNAs in lung adenocarcinoma (LUAD)-related competing endogenous RNA networks, and showed an independent prognostic value of overall survival for patients with LUAD ( Hou and Yao, 2021 ). FMR1 intronic transcript 1 (FMR1-IT1) is also known as FMR1 intronic transcript 1 (non-protein coding) or Fragile X Mental Retardation Syndrome Protein (FMRP) or FMR1, there were evidence that FMRP regulated tumor invasiveness-related pathways in melanoma cells by impacting cell migration, invasion and adhesion ( Zalfa et al, 2017 ), and its overexpression was associated with lung metastasis of murine breast cancer ( Lucá et al, 2013 ).…”

DataSheet2.XLSX

“…Among the nine GI-lncRNAs used for construction of the GI-lncRNA model, the biological functions of FAM83A (Wang et al, 2020;Zeng et al, 2020). Although the biological functions of AF131215.5 and RHOXF1-AS1 have not been reported in cancer, our results are in accordance with previous findings showing that these two lncRNAs are associated with the OS of LUAC (Hou and Yao, 2021). The remaining five lncRNAs have not been reported in lung cancer or other human cancers.…”

A innovative prognostic symbol based on neutrophil extracellular traps (NETs)-related lncRNA signature in non-small-cell lung cancer

“…Six NETs-related lncRNAs (AF131215.5, MYOSLID, NKILA, AC090152.1, SNHG10, and TRG.AS) have been reported to be associated with cancer progression. AF131215.5 was found to have an independent prognostic value of overall survival for patients with lung adenocarcinoma (LUAD) [ 24 ]. In terms of partial epithelial-mesenchymal transition (p-EMT), MYOSLID expression in head and neck squamous cell carcinoma (HNSCC) was closely correlated with Slug, PDPN, and LAMB3, and is a key regulator of tumor cell survival.…”