Tissue and serum metabolomic phenotyping for diagnosis and prognosis of hepatocellular carcinoma

Abstract

More than two‐thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography–mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.

An Inflammatory Response-Related Gene Signature Can Impact the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

“…However, we are often unable to make early diagnosis and predict the therapeutic effect of HCC due to the small number of useful biomarkers. Previous studies indicated that novel serum biomarkers including circulating tumor cells, circulating nucleic acids ( 19 ), and the combination of retinol and retinal panel ( 20 ) have excellent accuracy of HCC prognosis. In addition, inflammatory response-related serum biomarkers such as medium-granulocyte ratio, platelet-lymphoid ratio and lymphoid-monocyte ratio also have a good performance in predicting prognosis of HCC ( 10 ).…”

Identifying SLC27A5 as a potential prognostic marker of hepatocellular carcinoma by weighted gene co-expression network analysis and in vitro assays

“…Dysregulation of retinoids and relevant pathways have been observed in animal tumor models and human carcinoma cell lines [29]. Retinoids deficiency is associated with increased risk of carcinogenesis [30][31][32] and with poor prognosis of liver cancer [33]. Briefly, our data showed that metabolic pathway was highly associated with the prognosis of HCC.…”

Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis

“…Downregulated genes were enriched in the pathway of retinol metabolism, which was associated with the development of liver cancer. The decrease of retinol storage in the liver was observed in hepatocellular carcinoma patients [ 37 ]. A recent study revealed that the apoptosis pathway (Bax/Caspase) and cell cycle arrest pathway (P53/P21) could be activated after exposure to the alternating low-intensity and intermediate-frequency electric field in hepatocellular carcinoma spheroids [ 38 ].…”