Multiomics analysis demonstrated that TOPBP1 interacting checkpoint and Replication Regulator may serve as an immune-related biomarker indicative of poor prognosis in lung adenocarcinoma

Abstract

Background Lung adenocarcinoma (LUAD) persists as a leading contributor to global cancer-associated mortality. Identifying key oncogenic drivers is crucial for improving therapeutic strategies. This study aimed to investigate the role of TICRR in LUAD progression and its potential as a therapeutic target. Methods Hub genes were screened through integration of DepMap CRISPR-Cas9 data, TCGA expression profiles, and survival analysis. TICRR expressions was assessed in LUAD tissues, adjacent controls, and cell lines by RT-qPCR and immunohistochemistry. Functional roles were examined using MTT, colony formation, transwell, wound healing, and EdU assays in vitro . Bioinformatics analyses, including GSEA, somatic mutation profiling, immune correlation, CMap drug sensitivity, and CT-based radiomics, were performed to explore mechanisms, therapeutic potential and clinical correlation. Results TICRR expression was observed to be significantly elevated in LUAD tissues and cell lines, and its higher levels correlated with unfavorable patient outcomes and enrichment of malignant pathways, including EMT, E2F targets, and PI3K/AKT/mTOR signaling. High TICRR expression correlated with distinct somatic mutation patterns, increased tumor mutation burden, and elevated immune checkpoint expression. In vitro , TICRR knockdown suppressed Lung cancer progression. CMap analysis identified KU0063794 and CDK inhibitors as potential therapeutic agents targeting TICRR. Using a CT-based radiomics approach, the predictive model revealed a positive correlation between TICRR infiltration and radiological features in LUAD patients. Conclusion TICRR functions as a critical oncogenic driver in LUAD, promoting proliferation, invasion, and immune evasion. Targeting TICRR may represent a novel strategy for personalized treatment of LUAD.

Affiliated Institutions

• Tianjin Medical University General Hospital CN
• Chongqing Medical University CN
• Ningbo Medical Center Lihuili Hospital CN
• Ningbo University CN

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