Dataset Information

NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma.

ABSTRACT:

Background

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature.

Methods

Differentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on 1052 samples' data from our cohort, GEO and The Cancer Genome Atlas, we explored the relationship of clinicopathological features and NEIL3 expression to determine clinical effect of NEIL3 in LUAD. Western blotting (22 pairs of tumor and normal tissues), Real-time quantitative PCR (19 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis.

Results

This study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples (P < 0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p < 0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy.

Conclusions

This study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor of LUAD prognosis. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.

SUBMITTER: Zhao C

PROVIDER: S-EPMC8059184 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEnhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD.MethodsFirst, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman's correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer.ResultsAs a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types.ConclusionCollectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.