Background Previous studies have indicated that sarcopenia is associated with poor post-operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non-standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post-operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards. Methods A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post-operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post-operative complication, and the secondary outcome was the 90-day re-admission rate. Results A total of 155 patients [median age, 60.00 (IQR, 51.00-66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m 2 . The mean (SD) SMI of all participants was 47.05 ± 0.79 cm 2 /m 2 , and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post-operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P < 0.001). There was no difference in 90-day re-admission rates among the three groups. Sarcopenia (hazard ratio, 10.735; 95% CI, 2.547-45.244; P = 0.001) and open surgery (hazard ratio, 4.528; 95% CI, 1.425-14.387; P = 0.010) were independent risk factors associated with major complications. Conclusions Sarcopenia is associated with adverse outcomes after liver resection for HCC. It should be evaluated upon admission to classify high-risk patients and reduce the risk of major complications.

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

Background At present, immunotherapy has become an established treatment for cancer. Recently, we have realized that tumor metabolism has a huge impact on the shaping of immune reactivity in the tumor microenvironment (TME). Exploration of the tumor metabolic and immunocellular response reveals metabolic vulnerability as a therapeutic window for intervention to enhance immunotherapy. The clinical significance of glycolysis and its role in tumor-immune evolution have not been fully explored. Understanding the relationships between glycolysis, TME evolution and disease progression is of great significance for optimizing immunotherapy of liver cancer. Methods A glycolysis-related biomarker signature was initially identified in transcriptomic data within The Cancer Genome Atlas (TCGA, n=424). Predicted overall survival (OS) for the gene signature in the GSE54236 dataset (n=161) and our HCC cohort (n=132) was subsequently independently verified. The relative number of immune cells in the microenvironment was calculated using CIBERSORT. CCK-8, IHC, Transwell and Seahorse were used to assess the effects of a 3-gene signature on the malignant phenotype of liver cancer. Results A 3-gene signature of glycolysis significantly associated with poor OS was identified. Based on a multi-omics research strategy, we found the 3-gene signature was closely related to the evolution of liver cancer TME and disease progression, and was associated with liver cancer mutation load and immune evolution. High-risk patients have inhibition and depletion of the immune TME and immune escape through antigen presentation inhibition. Remarkably, the 3-gene signature can predict the clinical outcomes of HCC patients with different clinical subtypes. Conclusions Our investigation of the 3-gene signature provided evidence for tumor metabolism-immune co-evolution along HCC progression. The 3-gene signature for stratification of liver cancer risk has robust predictive power, both at the RNA and protein levels.