Abstract
BackgroundLung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature.MethodsDifferentially 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.ResultsThis 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.ConclusionsThis 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.
Highlights
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death
After an extensive literature review, we found that DNA endonuclease VIII-like 3 (NEIL3) is a very promising DNA repair gene
Tumor Immune Estimation Resource (TIMER) data showed that NEIL3 expression increased in 19 kinds of tumor tissues compared to adjacent normal tissues, especially in LUAD (Fig. 1c)
Summary
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. Lung cancer, accounting for almost one-quarter of all cancer deaths, has become more common than breast, brain, colorectal, and prostate cancers combined and is the leading cause of cancer-related death globally [1]. Lung adenocarcinoma (LUAD) is the most frequent pathological subtype, accounting for nearly 45% of lung cancer cases [2]. Patients with LUAD have improved overall survival (OS) after surgery and radiotherapy when diagnosed sooner. With the development of immune checkpoint inhibitors (atezolizumab, pembrolizumab, nivolumab, etc.), the survival of LUAD patients has significantly improved; such treatments have attracted considerable attention [5, 6]. Exploring and identifying effective immunerelated biomarkers for LUAD to reduce the mortality rates and develop innovative targeted therapies remains crucial
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
