ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicNovel Immune Markers and Predictive Models for Diagnosis, Immunotherapy and Prognosis in Lung CancerView all 3 articles
Multiomics analysis demonstrated that TOPBP1 Interacting Checkpoint And Replication Regulator may serve as an immune-related biomarker indicative of poor prognosis in lung adenocarcinoma
Provisionally accepted
Cangchang Shi1*
Chengbin Lin2
Ziyi Chen3
Wenbin Song1Long He4Hongyan Yu2Gaofeng Liang2Keyun Zhu2
Jinxian He2- 1Tianjin Medical University General Hospital, Tianjin, China
- 2Ningbo Medical Centre Lihuili Hospital, Ningbo, China
- 3Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- 4Bishan Hospital of Chongqing Medical University, Chongqing, China
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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.
Keywords: TICRR, Lung Adenocarcinoma, proliferation, invasion, Immune Evasion, Therapeutic target
Received: 05 Nov 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Shi, Lin, Chen, Song, He, Yu, Liang, Zhu and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cangchang Shi
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