Fig. 6: Identification of high-risk group-specific therapeutics for HCC. | npj Precision Oncology

Fig. 6: Identification of high-risk group-specific therapeutics for HCC.

From: Dual tissue mRNA and serum protein signatures improve risk stratification in hepatocellular carcinoma

Fig. 6

A Flowchart for in silico drug screening. B Differential drug sensitivity analysis between high- and low-risk HCC cell lines based on the LIMORE dataset. Yellow dots denote drugs with higher sensitivity in high-risk cell lines; blue dots denote drugs with higher sensitivity in low-risk cell lines. The statistical results were corrected using the Benjamini–Hochberg method. C Correlation of pharmacogenomic database-predicted drug AUC values with risk scores in TCGA-LIHC cohort. Negative correlation (yellow) implies greater drug sensitivity in high-risk patients. The statistical results were corrected using the Benjamini–Hochberg method. D Differences in predicted ABT-263 AUC values between risk groups across pharmacogenomic databases for TCGA-LIHC patients. E Expression levels of ABT-263 targets (from Drug Repurposing Hub) in high- vs. low-risk groups of TCGA-LIHC. F Colony formation assay evaluating responses to ABT-263 in high- and low-risk HCC cell lines. G Cell viability curves and IC50 values of ABT-263 in high- and low-risk HCC cell lines. H Flow cytometry analysis of apoptosis: proportions of early apoptotic (Annexin V+/PI−) and late apoptotic/necrotic (Annexin V+/PI+) cells in low-risk (Huh7) and high-risk (MHCC-97H) HCC cell lines, untreated or treated with ABT-263 (2 μM, 48 h). I Line graph illustrating tumor volume changes in the ABT-263 treatment group and the control group within Huh-7 and MHCC97H xenograft mouse models. J Images of tumors collected at the experimental endpoint. K Box plot illustrating the comparison of tumor weights at the experimental endpoint. ***p < 0.001; **p < 0.01; *p < 0.05; NS: p ≥ 0.05. FDR false discovery rate, CTRP Cancer Therapeutics Response Portal, GDSC Genomics of Drug Sensitivity in Cancer, HCC hepatocellular carcinoma, IC50 half-maximal inhibitory concentration, LIMORE liver cancer model repository, PI propidium iodide, PRISM profiling relative inhibition simultaneously in mixtures, TCGA The Cancer Genome Atlas.

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