Natural Killer Cell-Associated Radiogenomics Model for Hepatocellular Carcinoma: Integrating CD2 and Enhanced CT-Derived Radiomics Signatures

Rationale and objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. Natural Killer (NK) cells play a crucial role in immune defense against HCC, but their activity is often impaired by the tumor microenvironment (TME). This study aims to integrate radiomics and transcriptomics to develop a prognostic model linking NK cell characteristics to clinical outcomes in HCC.

Methods: Transcriptomic data from five cohorts (734 HCC patients) from the Gene Expression Omnibus and The Cancer Genome Atlas databases were analyzed using the Microenvironment Cell Populations-counter algorithm. NK cell-related prognostic biomarkers were identified via weighted gene co-expression network analysis and LASSO-Cox regression. Radiomics models were established using CT imaging features from 239 patients in three datasets from The Cancer Imaging Archive and Shanghai East Hospital. HCC radiogenomic subtypes were proposed by integrating genetic biomarkers and radiomics models.

Results: CD2 expression was identified as an independent NK cell-related prognostic biomarker, with a positive impact on prognosis and a strong correlation with NK cell-associated biological processes in HCC. A robust radiomics model was constructed, and the integration of CD2 expression with radioscore identified potential radiogenomic subtypes of HCC.

Conclusion: Radiomics has potential to link TME immune phenotypes with HCC prognosis. CD2 is a key biomarker connecting NK cells with radiomic features, offering a new classification of HCC into radiogenomic subtypes. This approach supports the use of radiogenomics in personalized HCC treatment.