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ATIC Promotes LIHC Progression and Serves as an Independent Prognostic Marker: A Pan-cancer Transcriptomic Analysis.
Hui Li1, Wentao Zhang1, Xiaojie Zhou1
1Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
Current Molecular Medicine
|May 19, 2026
Summary
The enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase (ATIC) is upregulated in many cancers, including liver hepatocellular carcinoma (LIHC), and serves as an independent prognostic biomarker. ATIC may guide targeted therapies in LIHC.
Area of Science:
- Oncology
- Biochemistry
- Genomics
Background:
- 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase (ATIC) is a bifunctional enzyme crucial for purine biosynthesis.
- ATIC's role in cancer progression is recognized, but its pan-cancer expression profile and prognostic significance in liver hepatocellular carcinoma (LIHC) require further elucidation.
Purpose of the Study:
- To investigate the pan-cancer expression, diagnostic, and prognostic utility of ATIC.
- To explore the association of ATIC with immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI).
- To develop and validate a prognostic nomogram for LIHC incorporating ATIC.
Main Methods:
- Analysis of TCGA RNA-seq data across 33 tumor types for ATIC expression, diagnostic accuracy (ROC/AUC), and prognostic associations (OS, DSS, PFI).
- Correlation analysis of ATIC with immune infiltration, TMB, MSI, and neoantigen load.
- Construction of a LIHC-specific prognostic nomogram and enrichment analyses (STRING, GO/KEGG, GSEA).
Main Results:
- ATIC was significantly upregulated in 16 cancer types, including LIHC, with high diagnostic accuracy (LIHC AUC=0.936).
- High ATIC expression correlated with poorer overall survival (OS) in LIHC (HR=1.39) and was linked to advanced T stage, higher grade, and elevated AFP.
- The ATIC-integrated nomogram demonstrated modest predictive accuracy for LIHC survival at 1, 3, and 5 years (AUCs 0.711, 0.649, 0.653).
Conclusions:
- ATIC is broadly upregulated in cancers, correlating with tumor progression and immune modulation, suggesting oncogenic roles.
- ATIC serves as an independent prognostic biomarker in LIHC, associated with specific signaling pathways (PI3K-AKT-mTOR, MYC) and predicting sensitivity to certain chemotherapeutics.
- ATIC holds potential as a biomarker for guiding targeted and chemotherapeutic strategies in LIHC, warranting further validation.
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