2. Academic Validation
  3. LMO2 confers value as a potential immunotherapy marker in pan-cancer analysis and inhibits progression of Clear Cell Renal Cell Carcinoma

LMO2 confers value as a potential immunotherapy marker in pan-cancer analysis and inhibits progression of Clear Cell Renal Cell Carcinoma

  • Transl Oncol. 2025 Jul:57:102409. doi: 10.1016/j.tranon.2025.102409.
Huiping Wang 1,  Cong Wang 2,  Jia Wei 3,  Xuan'er Zhao 4,  Xuemei Yang 5,  Renren Li 6,  Mengmeng Li 7,  Zhansheng Zhu 8
Affiliations

Affiliations

  • 1 Jiangsu Engineering Center for Precision Diagnosis and Treatment Research of Polygenic Diseases, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: hpw2013@xzhmu.edu.cn.
  • 2 Laboratory of Experimental and Clinical Pathology, Departments of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: congwangky2022@163.com.
  • 3 Laboratory of Experimental and Clinical Pathology, Departments of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: w2919868311@163.com.
  • 4 School of Anethesiology, Xuzhou Medical University, Xuzhou, Jiangs 221004, PR China. Electronic address: 646155143@qq.com.
  • 5 Laboratory of Experimental and Clinical Pathology, Departments of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: 1021318836@qq.com.
  • 6 Center of Healthcare Management, The Affiliated Maternity and Child Health Care Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: 100002013033@xzhmu.edu.cn.
  • 7 Department of Neurology III, Xuzhou Oriental People's Hospital, Xuzhou, Jiangsu 221004, PR China. Electronic address: 100002013081@xzhmu.edu.cn.
  • 8 Jiangsu Engineering Center for Precision Diagnosis and Treatment Research of Polygenic Diseases, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Laboratory of Experimental and Clinical Pathology, Departments of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: victorzhu2013@xzhmu.edu.cn.
PMID: 40344914 DOI: 10.1016/j.tranon.2025.102409
Abstract

Background: Emerging evidence highlights LIM-domain only 2 (LMO2) as both a potential biomarker and therapeutic target in diverse cancers. However, its functional characterization and clinical significance remain insufficiently explored in cancers such as Clear Cell Renal Cell Carcinoma (ccRCC). Therefore, comprehensive pan-cancer analysis and mechanistic investigation are necessary for optimizing LMO2-targeted immunotherapy strategies.

Methods: We conducted comprehensive multi-omics analyses and clinicopathological correlation studies across all cancers using TCGA data and specialized bioinformatics tools. Immune microenvironment associations were evaluated through Pearson correlation coefficients and TIMER algorithm validation. Subsequent functional enrichment analyses and predictive regulator identification were performed to delineate signaling pathways in ccRCC. Mechanistic insights were validated through in vitro models and xenograft experiments.

Results: LMO2 demonstrates significant deregulation across multiple malignancies, with its mRNA expression exhibiting distinct correlations with clinical staging, survival outcomes, and tumor immune microenvironment characteristics. Systematic analysis further confirmed it as a potentially novel immunotherapeutic target. Mechanistic investigations revealed that ZC3H13 depletion mediates LMO2 downregulation through N6-methyladenosine (m6A)-dependent epigenetic modifications. Through comprehensive functional validation in ccRCC, we established LMO2's tumor-suppressive properties using both in vitro models and xenograft assays. Subsequent pathway investigation demonstrated that LMO2 exerts its anti-tumor effects through direct modulation of the NF-κB signaling cascade via the GATA2-BEX1 regulatory axis.

Conclusions: Our findings establish substantial evidence for LMO2 as both a potential therapeutic candidate in Cancer Immunotherapy and a significant prognostic modulator in ccRCC pathogenesis. The mechanistic characterization of LMO2's tumor-suppressive functions warrants heightened translational consideration in both clinical management strategies and molecular etiology research.

Keywords

BEX-1; Bioinformatics; Cancer immunity; Lim-domain only 2; NF-κB; Prognosis; m(6)A.

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