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CT-based radiogenomic prediction of ICAM1 and RAET1E as biomarkers of NK cytotoxicity in clear cell renal cell carcinoma.

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Title: CT-based radiogenomic prediction of ICAM1 and RAET1E as biomarkers of NK cytotoxicity in clear cell renal cell carcinoma.
Authors: Ma X; Department of Radiology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.; Suzhou Key Laboratory for Integrated Stroke Prevention, Treatment, and Rehabilitation, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.; Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China., Yang J; Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China., Qian X; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China., Dou X; Department of Radiology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Ji S; Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China., Dai Y; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China., Yang Y; Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Wang Y; Department of Radiology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China., Zhu J; Department of Radiology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
Source: Frontiers in immunology [Front Immunol] 2026 Jun 03; Vol. 17, pp. 1773251. Date of Electronic Publication: 2026 Jun 03 (Print Publication: 2026).
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms: Killer Cells, Natural*/immunology , Intercellular Adhesion Molecule-1*/genetics , Intercellular Adhesion Molecule-1*/metabolism , Kidney Neoplasms*/immunology , Kidney Neoplasms*/diagnostic imaging , Kidney Neoplasms*/genetics , Carcinoma, Renal Cell*/immunology , Carcinoma, Renal Cell*/diagnostic imaging , Carcinoma, Renal Cell*/genetics , Biomarkers, Tumor*/genetics , Tomography, X-Ray Computed*/methods, Humans ; Female ; Male ; Radiomics ; Middle Aged ; Aged ; Cytotoxicity, Immunologic ; Prognosis
Abstract: Introduction: This study aims to develop a noninvasive CT-based radiogenomic framework to estimate imaging-associated biomarkers related to natural killer (NK) cell cytotoxicity in clear cell renal cell carcinoma (ccRCC). By linking imaging features to underlying molecular pathways, we address the limitations of invasive tissue sampling in assessing tumor heterogeneity and immune microenvironment.
Methods: This study analyzed preoperative contrast-enhanced CT images from 143 patients with histologically confirmed ccRCC and transcriptomic data from 538 TCGA-KIRC tumor samples. Radiomic features (3,176 per tumor) were extracted using PyRadiomics from manually segmented 3D tumor volumes (validated by two radiologists), spanning seven feature classes and eight image filters. Feature selection included variance filtering, the Mann-Whitney U test for gene-expression stratification (high/low groups), and redundancy removal via Pearson correlation analysis (|r| > 0.9), with AUC prioritization. An L1 -penalized support vector machine model with leave-one-out cross-validation was developed to estimate expression levels of ICAM1 and RAET1E, two NK cytotoxicity-related biomarkers. External validation was performed using tissue microarrays and immunohistochemistry from 26 independent ccRCC cases. Differential gene expression was assessed using edgeR (FDR < 0.05, fold-change > 2) and survival analysis via Cox regression.
Results: Transcriptomic analysis identified 835 imaging-associated genes enriched in immune-related pathways, with significant representation of the NK cell-mediated cytotoxicity pathway (KEGG, P < 0.05). Among candidate genes, ICAM1 and RAET1E demonstrated the strongest radiogenomic associations (AUC = 75.7% and 67.3%, respectively). Immunohistochemistry confirmed increased ICAM1 and decreased RAET1E expression in ccRCC tissues. Higher ICAM1 and lower RAET1E expression were associated with advanced tumor stage and unfavorable survival outcomes. External validation of the L1 -SVM model achieved predictive accuracies of 76.92% for ICAM1 and 73.08% for RAET1E, supporting the preliminary feasibility of this radiogenomic approach.
Conclusions: Our findings suggest that CT-derived radiomic features may provide noninvasive imaging correlates of biomarkers related to NK cytotoxicity-in ccRCC. Radiogenomic analysis of ICAM1 and RAET1E may provide a complementary exploratory framework for noninvasive immune characterization and biomarker research in ccRCC.
(Copyright © 2026 Ma, Yang, Qian, Dou, Ji, Dai, Yang, Wang and Zhu.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Contributed Indexing: Keywords: ICAM1; RAET1E; ccRCC; natural killer cell; radiogenomics
Substance Nomenclature: 126547-89-5 (Intercellular Adhesion Molecule-1)
0 (Biomarkers, Tumor)
0 (ICAM1 protein, human)
Entry Date(s): Date Created: 20260619 Date Completed: 20260619 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13272120
DOI: 10.3389/fimmu.2026.1773251
PMID: 42317355
Database: MEDLINE
Description
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1773251