Identification of small proline‐rich protein 1B (SPRR1B) as a prognostically predictive biomarker for lung adenocarcinoma by integrative bioinformatic analysis

• Published in: Thoracic cancer 2021-03, Vol.12 (6), p.796-806
• Main Authors: Zhang, Zihe, Shi, Ruifeng, Xu, Songlin, Li, Yongwen, Zhang, Hongbing, Liu, Minghui, Zhu, Guangsheng, Chen, Chen, Pan, Zhenhua, Liu, Hongyu, Chen, Jun
• Format: Article
• Language: English
• Subjects: Apoptosis; Bioinformatics; biomarker predictor; Biomarkers; Cell adhesion & migration; Cell cycle; Cold; Gene expression; Genomes; Lung cancer; Medical prognosis; non‐small cell lung cancer (NSCLC); Original; prognosis; Proteins; Regression analysis; small proline‐rich protein 1B (SPRR1B); Tumors
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.13836

Background With the ongoing development of targeted therapy and immunotherapy in recent years, the overall five‐year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues. Methods Lung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co‐expression network analysis (WGCNA) and protein–protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively. Results A total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer. Conclusions Our findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma. Identification of modules representing the associations between lung adenocarcinoma and normal tissue