Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies. Recent studies reveal that tumor microenvironment (TME) components significantly affect HCC growth and progression, particularly the infiltrating stromal and immune cells. Thus, mining of TME-related biomarkers is crucial to improve the survival of patients with HCC. Public access of The Cancer Genome Atlas (TCGA) database allows convenient performance of gene expression-based analysis of big data, which contributes to the exploration of potential association between genes and prognosis of a variety of malignancies, including HCC. The “Estimation of STromal and Immune cells in MAlignant Tumors using Expression data” algorithm renders the quantification of the stromal and immune components in TME possible by calculating the stromal and immune scores. Differentially expressed genes (DEGs) were screened by dividing the HCC cohort of TCGA database into high- and low-score groups according to stromal and immune scores. Further analyses of functional enrichment and protein-protein interaction networks show that the DEGs are mainly involved in immune response, cell adhesion, and extracellular matrix. Finally, seven DEGs have significant association with HCC poor outcomes. These genes contain FABP3, GALNT5, GPR84, ITGB6, MYEOV, PLEKHS1, and STRA6 and may be candidate biomarkers for HCC prognosis.

Background: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of hepatocellular carcinoma (HCC) patients especially with severe fibrosis. Methods: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. Results: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). Conclusion: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.

The present study was aimed at identifying the potential prognostic biomarkers of the immune‐related long noncoding RNA (IRL) signature for patients with hepatocellular carcinoma (HCC). RNA‐sequencing data and clinical information about HCC were obtained from The Cancer Genome Atlas. The IRLs were determined with regard to the coexpression of immune‐related genes and differentially expressed lncRNAs. The survival IRLs were obtained using the univariate Cox analysis. Subsequently, the prognosis model was constructed via the multivariate Cox analysis. Subsequently, functional annotation was conducted using Gene Set Enrichment Analysis (GSEA) and principal component analysis (PCA). In total, 341 IRLs were identified, and 6 IRLs were found to have a highly significant association with the prognosis of patients with HCC. The immune prognosis model was constructed with these 6 IRLs (AC099850.4, negative regulator of antiviral response, AL031985.3, PRRT3‐antisense RNA1, AL365203.2, and long intergenic nonprotein coding RNA 1224) using the multivariate Cox regression analysis. In addition, immune‐related prognosis signatures were confirmed as an independent prognostic factor. The association between prognostic signatures and immune infiltration indicated that the 6 lncRNAs could reflect the immune status of the tumor. Collectively, the present study demonstrates that six‐lncRNA signatures may be potential biomarkers to predict the prognosis of patients with HCC.

Background: Hypoxia is a key factor in the development of hepatocellular carcinoma (HCC), which is the most common primary liver cancer with poor prognosis. The current study aimed to identify the potential prognostic biomarkers of the hypoxia-associated gene signature in patients with HCC, and to further explore the relationship between hypoxia and immune infiltration. Methods: After the determination of differentially expressed genes (DEGs) using the HCC transcriptome data of The Cancer Genome Atlas database and hypoxia-related gene set, the prognosis-associated genes were identified using univariate Cox regression analysis. Then, the hypoxia prognosis model was established via multivariate Cox regression analysis, with functional annotation conducted using Gene Set Enrichment Analysis. CIBERSORT was utilized to analyze the degree of tumor immune invasion, and an International Cancer Genome Consortium cohort to verify the reliability of the prognosis model. Expression levels of hypoxia-associated genes were detected by real-time quantitative polymerase chain reaction in HCC samples. Results: 3 genes (ENO1, SAP30, and STC2) constructed the hypoxia prognosis model. The patients were subdivided into 2 groups based on median risk score, with a high hypoxic score indicating poor prognosis of HCC. The hypoxia signature could be employed as an independent prognostic factor in HCC. In addition, the proportion of macrophages was higher in the high-risk group. Conclusion: The hypoxia-associated signature could be a potential prognostic marker of HCC and provides a different perspective for immunotherapy of HCC.

The interactions and adaptive responses of liver and kidney xenografts within the same recipient remain poorly understood. Therefore, we transplanted an auxiliary liver and a heterotopic kidney from one six-gene-edited pig into a human decedent. Longitudinal blood profiling was integrated with source-resolved single-cell transcriptomics, chromatin accessibility, spatial and proteomic analyses. Blood analyses revealed recurrent neutrophil-rich intervals with early degranulation and interleukin-1 signalling, followed by late monocyte recruitment, antigen-presentation and interferon programmes. Recipient-derived liver innate immune cells are C1Q-dominant at day 3 and 98.2% SPP1/TREM2 macrophages at day 11, whereas kidney innate cells remained enriched for C1Q macrophages and monocytes. In the porcine kidney, SPP1/TREM2 macrophage programmes localized to injured tubular and collecting-duct niches. Bile and urine production emerged on distinct timelines despite persistent tissue injury. In summary, these findings reveal distinct organ-specific xenograft responses despite a shared systemic environment, suggesting organ-specific genetic engineering and providing a framework for future optimization of xenogeneic organs.

Situs inversus totalis (SIT) alters graft positioning and vascular reconstruction during liver transplantation. A 56-year-old man with SIT, decompensated hepatitis B cirrhosis and hepatocellular carcinoma received a 558-g deceased-donor whole-liver graft, with a graft-to-recipient weight ratio of 0.60%. The graft was implanted in the native left-sided hepatic fossa in a reversed orientation. Postoperative CT showed a large splenorenal shunt and heterogeneous graft enhancement. Portal vein velocity fell from 44.7 cm/s on postoperative day (POD) 1 to 25 cm/s on POD3–4 and was 32 cm/s on POD5. Endovascular occlusion was abandoned on POD5 because venography showed aneurysmal dilatation and the procedural risk was judged excessive. Open ligation of the approximately 3-cm shunt was performed on POD6, preserving the main renal vein. Portal vein velocity was 30 cm/s after ligation, 37 cm/s on POD7 and 42 cm/s on POD9. Total bilirubin decreased from 158.6 μmol/L on POD4 to 70.5 μmol/L on POD13; the international normalized ratio was 1.49 on POD6 and 1.02 on POD14. The patient was discharged on POD27. Imaging showed no tumor recurrence at approximately 19 months, and alpha-fetoprotein was 7.32 ng/mL at approximately 23 months. This case describes surgical treatment of suspected portal steal in an SIT recipient when endovascular shunt occlusion was unsuitable.