Objectives To develop and validate a pre-transcatheter arterial chemoembolization (TACE) MRI-based radiomics model for predicting tumor response in intermediate-advanced hepatocellular carcinoma (HCC) patients. Materials Ninety-nine intermediate-advanced HCC patients (69 for training, 30 for validation) treated with TACE were enrolled. MRI examinations were performed before TACE, and the efficacy was evaluated according to the mRECIST criterion 3 months after TACE. A total of 396 radiomics features were extracted from T2-weighted pre-TACE images, and least absolute shrinkage and selection operator (LASSO) regression was applied to feature selection and model construction. The performance of the model was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results The AFP value, Child-Pugh score, and BCLC stage showed a significant difference between the TACE response (TR) and non-TACE response (nTR) patients. Six radiomics features were selected by LASSO and the radiomics score (Rad-score) was calculated as the sum of each feature multiplied by the non-zero coefficient from LASSO. The AUCs of the ROC curve based on Rad-score were 0.812 and 0.866 in the training and validation cohorts, respectively. To improve the diagnostic efficiency, the Rad-score was further integrated with the above clinical indicators to form a novel predictive nomogram. Results suggested that the AUC increased to 0.861 and 0.884 in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. Conclusion The radiomics and clinical indicator-based predictive nomogram can well predict TR in intermediate-advanced HCC and can further be applied for auxiliary diagnosis of clinical prognosis. Key Points • The therapeutic outcome of TACE varies greatly even for patients with the same clinicopathologic features. • Radiomics showed excellent performance in predicting the TACE response. • Decision curves demonstrated that the novel predictive model based on the radiomics signature and clinical indicators has great clinical utility.
Background Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. Methods Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. Results Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvβ3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvβ3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. Conclusions Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC.
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