NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma

Cancer Cell International

Jian Liu¹  Xuewen Chen²  Yifei Liu³  Hui Sun³  Jianguo Zhang³  Tingting Bian³  Lei Liu³  Xin Qian⁴  Cui Zhao⁴  Miaosen Zheng⁴  Haomiao Zhou⁴ 

[1] Department of Chemotherapy, Affiliated Hospital of Nantong University;Department of Orthopedics, Second People’s Hospital of Jingmen;Department of Pathology, Affiliated Hospital of Nantong University;Nantong University;

关键词: Bioinformatics;    Lung adenocarcinoma;    NEIL3;    Real-time quantitative PCR;    Immunohistochemistry;    Prognostic signature;   

DOI  :  10.1186/s12935-021-01938-4

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown