Prognostic signature based on S100 calcium-binding protein family members for lung adenocarcinoma and its clinical significance.

Comput Methods Biomech Biomed Engin

Academician Expert Workstation of Zhejiang Luoxi Medical Technology Co., Ltd., Hangzhou, China.

Published: July 2024

AI Article Synopsis

  • The S100 family proteins are linked to cancer progression and could serve as biomarkers, but their role in lung adenocarcinoma (LUAD) prognosis is not well understood.
  • Researchers analyzed LUAD patient data from the TCGA database to study S100 genes, identifying two patient clusters with differing overall survival rates through clustering and survival analysis.
  • An 11-gene prognostic signature was developed using regression analysis, demonstrating strong predictive capabilities, and led to the discovery of small molecular compounds that may target these genes for effective treatment.

Article Abstract

The S100 family proteins (S100s) participate in multiple stages of tumorigenesis and are considered to have potential value as biomarkers for detecting and predicting various cancers. But the role of S100s in lung adenocarcinoma (LUAD) prognosis is elusive. Transcriptional data of LUAD patients were retrieved from TCGA, and relevant literature was extensively reviewed to collect S100 genes. Differential gene expression analysis was performed on the LUAD data, followed by intersection analysis between the differentially expressed genes (DEGs) and S100 genes. Unsupervised consensus clustering analysis identified two clusters. Significant variations in overall survival between the two clusters were shown by Kaplan-Meier analysis. DEGs between the two clusters were analyzed using Lasso regression and univariate/multivariate Cox regression analysis, leading to construction of an 11-gene prognostic signature. The signature exhibited stable and accurate predictive capability in TCGA and GEO datasets. Subsequently, we observed distinct immune cell infiltration, immunotherapy response, and tumor mutation characteristics in high and low-risk groups. Finally, small molecular compounds targeting prognostic genes were screened using CellMiner database, and molecular docking confirmed the binding of AMG-176, Estramustine, and TAK-632 with prognostic genes. In conclusion, we generated a prognostic signature with robust and reliable predictive ability, which may provide guidance for prognosis and treatment of LUAD.

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Source
http://dx.doi.org/10.1080/10255842.2024.2376668DOI Listing

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