Phys Med Biol. 2026 Mar 13. doi: 10.1088/1361-6560/ae5209. Online ahead of print.

ABSTRACT

ObjectiveThis study aims to develop a functional-based multi-omics model for early prediction of radiation pneumonitis (RP) by extracting radiomic and dosiomic features from functionally defined lung regions, using generated perfusion (Q) and ventilation (V) from pre-radiotherapy planning computed tomography (CT).
ApproachWe retrospectively analyzed data from 121 patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative-intent IMRT between 2015 and 2019, including pre-treatment CT and dose maps. Q and V maps were generated from CT with deep learning-based and supervoxel-based approaches, respectively. Regions of interest (ROIs) combined the planning target volume (PTV) with each of three functional lung regions-high functional lung (HFL), low functional lung (LFL), and whole lung (WL)-defined by thresholds on Q and V maps. Radiomic and dosiomic features were extracted from CT and dose distributions within each ROI. For each ROI, For each ROI, three methods-radiomics (R), dosiomics (D), and dual-omics (RD)-were constructed. 13 machine learning algorithms were trained and evaluated using 10-fold cross-validation, and model performance was assessed by the average area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. RP was defined as CTCAE grade ≥ 2.
Main resultsOf the 35 selected features, 20 were from HFL. In dual-omics models, using HFL features improved predictive performance for RP (AUC 0.879±0.105) compared to WL (AUC 0.778 ± 0.100). In HFL, the RD method outperformed both R (AUC 0.786± 0.076) and D (AUC 0.791 ± 0.107) methods. Decision curve analysis showed the dual-omics model based on HFL provided the highest net benefit across threshold probabilities.
SignificanceThis study is the first to systematically demonstrate that features extracted from CT-derived HFL capture important functional differences and provide strong predictive value for RP. Compared to conventional methods, integrating radiomics, dosiomics, and CT-based functional information further improves predictive performance.&#xD.

PMID:41825133 | DOI:10.1088/1361-6560/ae5209

Phys Med Biol. 2026 Mar 13. doi: 10.1088/1361-6560/ae5209. Online ahead of print.

ABSTRACT

ObjectiveThis study aims to develop a functional-based multi-omics model for early prediction of radiation pneumonitis (RP) by extracting radiomic and dosiomic features from functionally defined lung regions, using generated perfusion (Q) and ventilation (V) from pre-radiotherapy planning computed tomography (CT).
ApproachWe retrospectively analyzed data from 121 patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative-intent IMRT between 2015 and 2019, including pre-treatment CT and dose maps. Q and V maps were generated from CT with deep learning-based and supervoxel-based approaches, respectively. Regions of interest (ROIs) combined the planning target volume (PTV) with each of three functional lung regions-high functional lung (HFL), low functional lung (LFL), and whole lung (WL)-defined by thresholds on Q and V maps. Radiomic and dosiomic features were extracted from CT and dose distributions within each ROI. For each ROI, For each ROI, three methods-radiomics (R), dosiomics (D), and dual-omics (RD)-were constructed. 13 machine learning algorithms were trained and evaluated using 10-fold cross-validation, and model performance was assessed by the average area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. RP was defined as CTCAE grade ≥ 2.
Main resultsOf the 35 selected features, 20 were from HFL. In dual-omics models, using HFL features improved predictive performance for RP (AUC 0.879±0.105) compared to WL (AUC 0.778 ± 0.100). In HFL, the RD method outperformed both R (AUC 0.786± 0.076) and D (AUC 0.791 ± 0.107) methods. Decision curve analysis showed the dual-omics model based on HFL provided the highest net benefit across threshold probabilities.
SignificanceThis study is the first to systematically demonstrate that features extracted from CT-derived HFL capture important functional differences and provide strong predictive value for RP. Compared to conventional methods, integrating radiomics, dosiomics, and CT-based functional information further improves predictive performance.&#xD.

PMID:41825133 | DOI:10.1088/1361-6560/ae5209

NPJ Precis Oncol. 2026 Mar 11. doi: 10.1038/s41698-026-01372-7. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, and its progression is closely linked to the establishment of an immunosuppressive tumor microenvironment. Myristoylated alanine-rich C kinase substrate (MARCKS) has been implicated in tumor biology; however, its role in regulating immune interactions in HCC remains poorly defined. Here, we performed an integrated multi-omics analysis combining bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics to systematically investigate the expression pattern and functional relevance of MARCKS in HCC. We found that MARCKS was significantly upregulated in HCC tissues and that high MARCKS expression was associated with aggressive clinicopathological features and unfavorable prognosis. Single-cell and spatial analyses revealed that MARCKS expression was enriched in myeloid cell populations within the tumor microenvironment. Functional annotation and mIF(Multiple immunofluorescence) validation demonstrated that MARCKS expression was associated with enhanced JAK/STAT3 signaling and M2-like macrophage polarization. Consistently, MARCKS silencing in HCC cell lines reduced STAT3 phosphorylation, suppressed malignant phenotypes in vitro, inhibited tumor growth in vivo, and diminished the capacity of tumor-derived conditioned media to promote macrophage M2 polarization. Together, these findings identify MARCKS as a key regulator of the immunosuppressive tumor microenvironment in HCC and highlight its potential as a therapeutic target for overcoming immune evasion.

PMID:41813922 | DOI:10.1038/s41698-026-01372-7