From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma

Abstract

BackgroundLiver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis.MethodsFrom the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1’s link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models’ discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves.ResultsOur findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1’s potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration.ConclusionThis study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC’s complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

Leveraging radiomics and AI for precision diagnosis and prognostication of liver malignancies

“…Preliminary works have indicated the potential of radiomics quantification in immune profiling for HCC. Notably, these works studied expression of vascular endothelial growth factor (VEGF) ( 56 ), angiopoietin-2 ( 57 ), Forkhead Box M1 (FOXM1) ( 58 ), and Ki-67 ( 59 , 60 ). Additionally, the presence of β-catenin mutation ( 61 ), intra-tumoral tertiary lymphoid structures ( 62 ), cytokeratin 19 ( 63 , 64 ), glypican-3 (GPC3) ( 65 ), immunohistochemical cell type markers for T-cells (CD3), macrophages (CD68) and endothelial cells (CD31), PD1 and CTLA4 at mRNA expression level ( 66 ), as well as density of CD3+ and CD8+ T cells ( 67 ) were studied.…”

“…Each of these immune subtypes plays a critical role in unraveling the complex immune response within HCC, providing insights for prognostication and targeted therapeutic interventions. AUCs of these tasks fell somewhere between 0.76 to 0.95 (56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). Notably, when clinical factors were integrated with radiomics signatures, models' performance significantly improved.…”

The roles of cancer stem cell-derived secretory factors in shaping the immunosuppressive tumor microenvironment in hepatocellular carcinoma

“…The implicated metabolic regulators include XOR ( 88 ), SCD1 ( 89 ), and ACLY ( 90 ). Finally, transcription factors involved in regulating cancer stemness in HCC, such as SALL4 ( 80 ) and FOXM1 ( 91 ), are known to exert immunosuppressive effects on the TME of HCC.…”