Overexpression of ANAPC1 Affects the Cell Cycle Pathway to Promote theProgression of Lung Adenocarcinoma

BACKGROUND: Anaphase-Promoting Complex Subunit 1 (ANAPC1) plays a critical regulatory role in cell mitosis and is also an important contributor to tumorigenesis. However, its specific function in Lung Adenocarcinoma (LUAD) has not yet been systematically investigated. AIMS: This research aims to evaluate the expression and clinicopathological significance of ANAPC1 in LUAD, and to explore its molecular mechanisms and biological functions. METHODS: A total of 4,813 samples from multiple databases were integrated to assess ANAPC1 mRNA expression. Additionally, 122 clinical samples were collected to detect ANAPC1 protein expression via immunohistochemistry. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening assessed the ANAPC1 knockout effect in LUAD cell lines. Enrichment and immune-related analyses were conducted to explore the molecular basis of ANAPC1 in LUAD. The prognostic value of ANAPC1 was assessed using Kaplan-Meier curves and Cox regression models. Finally, immunoassay, drug concentration, and molecular docking for ANAPC1 were calculated. RESULTS: ANAPC1 mRNA was significantly upregulated in LUAD (SMD = 0.74, 95% CI [0.41; 1.07]; AUC = 0.82 [0.79-0.85]), and overexpression was confirmed at the protein level (p < 0.0001, AUC: 0.999 [0.996-1.000]). CRISPR screening showed that ANAPC1 knockout in 19 LUAD cell lines inhibited cell growth. Most high-expression co-expressed genes associated with ANAPC1 were primarily enriched in cell cycle and mitosis pathways. ANAPC1 expression correlated with immune cell infiltrations and was identified as a prognostic risk factor in LUAD (HR = 1.42, 95% CI: 1.02-1.98). Patients with high ANAPC1 expression exhibited lower immune phenotype scores and higher tumor immune dysfunction and exclusion scores. Higher ANAPC1 expression showed lower predicted drug concentrations (docetaxel, paclitaxel, gefitinib, and crizotinib) Conclusions: Upregulated ANAPC1 expression in LUAD patients indicates potential predictive value for poor prognosis. Overexpression of ANAPC1 may contribute to LUAD progression by promoting cell growth and altering the cell cycle.