Elevated expression of ANAPC1 in lung squamous cell carcinoma: clinical implications and mechanisms

Abstract

Aim: To investigate the comprehensive expression levels and possible molecular mechanisms of Anaphase Promoting Complex Subunit 1 (ANAPC1) in lung squamous cell carcinoma (LUSC). Methods: Data from 2,031 samples were combined to evaluate ANAPC1 mRNA levels, and 118 samples were collected for immunohistochemical (IHC) analysis. High-expression co-expressed genes (HECEGs) associated with ANAPC1 were analyzed for signaling pathways. Clinical significance, immune computations, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) validation of ANAPC1’s role in LUSC were assessed. Molecular docking evaluated binding affinity with potential therapeutics. Results: ANAPC1 mRNA was significantly upregulated in LUSC (SMD = 1.97, 95% CI [1.26–2.67]). Protein-level analysis confirmed this upregulation (p < 0.001). Most HECEGs associated with ANAPC1 were enriched in cell cycle pathways. Higher ANAPC1 expression correlated with poorer survival in LUSC patients (HR = 1.11, 95% CI: 1–1.49). ANAPC1 expression was higher in males and N1-stage vs. females and N0-stage; lower in grade I vs. II/III. Overexpression reduces immune cell infiltration and immunotherapy effectiveness, while knockdown inhibits cell proliferation. Drug sensitivity and docking analyses identified tenovin-1, carboxyatractyloside, and phycocyanobilin as potential antitumor agents targeting ANAPC1. Conclusion: The elevated expression of ANAPC1 might play a role in LUSC advancement and progression through its participation in cell growth-related pathways.