DOI: 10.6084/m9.figshare.28776505
title: Elevated expression of ANAPC1 in lung squamous cell carcinoma: clinical implications and mechanisms

description: To investigate the comprehensive expression levels and possible molecular mechanisms of Anaphase Promoting Complex Subunit 1 (ANAPC1) in lung squamous cell carcinoma (LUSC). 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. ANAPC1 mRNA was significantly upregulated in LUSC (SMD = 1.97, 95% CI [1.26–2.67]). Protein-level analysis confirmed this upregulation (<i>p</i> &lt; 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. The elevated expression of ANAPC1 might play a role in LUSC advancement and progression through its participation in cell growth-related pathways. This study looks at over 2000 samples and shows that a protein called ANAPC1 is found in higher amounts in lung squamous cell carcinoma (LUSC). The study finds that higher levels of ANAPC1 are associated with poorer survival outcomes and are more commonly observed in males and at later stages of the disease. Lower levels of ANAPC1 might help patients respond better to immunotherapy. The study also shows that removing ANAPC1 slows down cancer cell growth and identifies possible compounds that could target ANAPC1, offering hope for new therapies for LUSC. The High expression of ANAPC1 in lung squamous cell carcinoma (LUSC) has been demonstrated at both the mRNA and protein levels.Most of the highly expressed co-expressed genes (HECEGs) of ANAPC1 are enriched in pathways related to cell growth.Elevated ANAPC1 levels in LUSC are significantly associated with reduced immune cell infiltration.In LUSC patients, higher ANAPC1 expression is associated with poorer prognosis.ANAPC1 expression levels are higher in male patients, those at N1 stage, and those with Pathology grade I, compared to female patients, those at N0 stage, and those with Pathology grades II/III, respectively.Based on in silico analyses, knockdown of ANAPC1 may inhibit the proliferation of LUSC cells. The High expression of ANAPC1 in lung squamous cell carcinoma (LUSC) has been demonstrated at both the mRNA and protein levels. Most of the highly expressed co-expressed genes (HECEGs) of ANAPC1 are enriched in pathways related to cell growth. Elevated ANAPC1 levels in LUSC are significantly associated with reduced immune cell infiltration. In LUSC patients, higher ANAPC1 expression is associated with poorer prognosis. ANAPC1 expression levels are higher in male patients, those at N1 stage, and those with Pathology grade I, compared to female patients, those at N0 stage, and those with Pathology grades II/III, respectively. Based on in silico analyses, knockdown of ANAPC1 may inhibit the proliferation of LUSC cells.