Imaging Exploration of Molecular Subtypes in Tongue Squamous Cell Carcinoma

TL;DR

This study demonstrates that radiomic features from preoperative imaging can non-invasively distinguish molecular subtypes of tongue squamous cell carcinoma, linking imaging phenotypes with underlying biological differences.

Contribution

It introduces an integrated transcriptomic-radiomics framework to identify and differentiate molecular subtypes of TSCC using non-invasive imaging features.

Findings

Two stable molecular subtypes, C1 and C2, identified with distinct biological pathways.

Ten radiomic features significantly differed between subtypes, mainly wavelet-derived texture features.

Radiomics shows potential for non-invasive molecular characterization of TSCC.

Abstract

Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with marked biological heterogeneity and variable clinical outcomes. Although molecular profiling has improved understanding of TSCC heterogeneity, its clinical use remains constrained by invasive tissue sampling and limited representation of whole-tumor spatial complexity. Meanwhile, most radiomics studies in TSCC have focused on downstream clinical endpoints, and whether imaging can non-invasively reflect intrinsic molecular subtypes remains unclear. In this study, an integrated transcriptomic-radiomics framework was used to investigate the relationship between preoperative imaging phenotypes and molecular subtypes in TSCC. Transcriptomic data from 60 TSCC cases in The Cancer Genome Atlas were analyzed using unsupervised consensus clustering, followed by differential expression and functional enrichment analyses. Matched preoperative imaging data from The Cancer Imaging Archive were manually annotated for primary tumor regions, and radiomic features were extracted using PyRadiomics; group differences were assessed with the U-test. Two stable molecular subtypes, C1 and C2, were identified. Their biological differences were mainly associated with squamous epithelial differentiation, inflammatory signaling, and lipid metabolism, with C2 showing greater enrichment of immune-related pathways. In addition, 10 radiomic features differed significantly between the two subtypes, mainly wavelet-derived texture features from gray-level size zone, dependence, co-occurrence, and run length matrices (P=0.00202-0.0162). These findings support the potential of radiomics as a non-invasive approach for characterizing molecular heterogeneity in TSCC and provide an initial radiogenomic framework for biologically informed preoperative assessment.