Identification and validation of a prognostic-related mutant gene DNAH5 for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and has a poor prognosis. Thus, there is a need for an effective biomarker to improve and predict the prognosis of HCC. Methods: RNA sequencing data, simple nucleotide variation data, and clinical data of HCC patients from The Cancer Genome Atlas (TCGA) to identify mutant genes, simple nucleotide variation data, and clinical data of HCC patients from the International Cancer Genome Consortium (ICGC) to validate the prognostic value of mutant genes were the data sources of the present study. To identify the overall survival (OS)-related mutant genes, a Kaplan-Meier (KM) analysis was conducted. We carried out univariate Cox and multivariate Cox regression analyses to identify the independent prognostic factors. We also conducted a correlation analysis of immune cells and mutant genes. To explore the molecular mechanisms of mutant genes, we conducted a gene set enrichment analysis (GSEA). A nomogram was constructed to help predict the prognosis of HCC. In addition, we explored the expression profile of mutant genes in HCC based on a TCGA dataset, an ICGC dataset, and our own HCC tissue samples. Results: We identified and validated a mutant gene, dynein axonemal heavy chain 5 (DNAH5), which was negatively related to the OS of HCC patients. Univariate Cox and multivariate Cox regression analyses revealed that the mutant gene DNAH5 could act as an independent prognostic factor for HCC. Most pathways of the mutant gene DNAH5 were involved in cancer development and progression based on GSEA analysis. The mutant gene DNAH5 was negatively correlated with monocytes, naive CD4 T cells, activated dendritic cells, and activated mast cells. In addition, the mRNA and protein levels of DNAH5 had a significantly higher level of expression in the tissue samples of patients with HCC. A nomogram consisting of the pathological stage, DNAH5, and tumor mutation burden (TMB) performed well. Conclusion: The mutant gene DNAH5 had a significantly higher level of expression in the tissue samples of patients with HCC, could act as an independent prognostic factor for HCC, and is a potential new immunotherapy target for HCC.

Study of the Intersegmental Veins Between S5 and S8 Based on 3D Reconstruction.

BACKGROUND: Anatomic resection (AR) is a surgical method for treating hepatocellular carcinoma, and identifying intersegmental planes between segments 5 (S5) and 8 (S8) remains challenging. This study aims to find reliable intersegmental veins (IVs) between them as anatomical landmarks using 3D reconstruction analysis. METHODS: We retrospectively evaluated 57 patients who underwent multidetector-row CT scans from September 2021 to January 2023. The portal vein watershed of S5 and S8 and hepatic veins were reconstructed using 3D reconstruction analysis software. We counted and analyzed the IVs running within the intersegmental plane between S5 and S8, examined their features, and analyzed the location of the junctions between IVs and middle hepatic veins (MHVs). RESULTS: Among the 57 patients, 43 patients (75.4%) had IVs between S5 and S8. Most patients (81.4%) had a single IV joining the MHV, while 13.9% had two IVs, one joining the MHV and the other joining the right hepatic vein (RHV). The majority of IV-MHV junctions were found in the lower part of the MHVs. The most clearly identifiable junctions between the IVs and MHVs occurred slightly below the midpoint of the horizontal planes of the second hepatic portal and the center of the gallbladder bed. CONCLUSION: Our study identified IVs between S5 and S8 in the liver as potential anatomical landmarks during AR for hepatocellular carcinoma surgery. We found three types of IVs and provided insights on how to locate their junctions with MHVs for easier surgical navigation. However, individual anatomical variations must be considered, and preoperative 3D reconstruction and personalized surgical planning are crucial for success. More research with larger sample sizes is needed to validate our findings and establish the clinical significance of these IVs as landmarks for AR.

Genomic Instability of Mutation-Derived Gene Prognostic Signatures for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the major cancer-related deaths worldwide. Genomic instability is correlated with the prognosis of cancers. A biomarker associated with genomic instability might be effective to predict the prognosis of HCC. In the present study, data of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were used. A total of 370 HCC patients from the TCGA database were randomly classified into a training set and a test set. A prognostic signature of the training set based on nine overall survival (OS)-related genomic instability-derived genes (SLCO2A1, RPS6KA2, EPHB6, SLC2A5, PDZD4, CST2, MARVELD1, MAGEA6, and SEMA6A) was constructed, which was validated in the test and TCGA and ICGC sets. This prognostic signature showed more accurate prediction for prognosis of HCC compared with tumor grade, pathological stage, and four published signatures. Cox multivariate analysis revealed that the risk score could be an independent prognostic factor of HCC. A nomogram that combines pathological stage and risk score performed well compared with an ideal model. Ultimately, paired differential expression profiles of genes in the prognostic signature were validated at mRNA and protein level using HCC and paratumor tissues obtained from our institute. Taken together, we constructed and validated a genomic instability-derived gene prognostic signature, which can help to predict the OS of HCC and help us to explore the potential therapeutic targets of HCC.

A Prognostic Autophagy-Related Gene Pair Signature and Small-Molecule Drugs for Hepatocellular Carcinoma.

Dysregulation of autophagy-related genes (ARGs) is related to the prognosis of cancers. However, the aberrant expression of ARGs signature in the prognosis of hepatocellular carcinoma (HCC) remain unclear. Using The Cancer Genome Atlas and the International Cancer Genome Consortium database, 188 common autophagy-related gene pairs (ARGPs) were identified. Through univariate, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis, a prognostic signature of the training set was constructed on the basis of 6 ARGPs. Further analysis revealed that the ARGP based signature performed more accurately in overall survival (OS) prediction compared to other published gene signatures. In addition, a high risk of HCC was closely related to CTLA4 upregulation, LC3 downregulation, low-response to axitinib, rapamycin, temsirolimus, docetaxel, metformin, and high-response to bleomycin. Univariate Cox and multivariate Cox analysis revealed that the risk score was an independent prognostic factor for HCC. These results were internally validated in the test and TCGA sets and externally validated in the ICGC set. A nomogram, consisting of the risk score and the TNM stage, performed well when compared to an ideal nomogram. In conclusion, a 6-ARGP-based prognostic signature was identified and validated as an effective predictor of OS of patients with HCC. Furthermore, we recognized six small-molecule drugs, which may be potentially effective in treating HCC.

[Efficiency of isolated caudate lobe resection for huge hepatocellular carcinoma (10 cm or larger in diameter)].

OBJECTIVE: To explore the feasibility and efficacy of isolated caudate lobe resection for caudate lobe in huge hepatocellular carcinoma(10 cm or larger in diameter).
 Methods: Clinical data of 27 patients with hepatocellular carcinoma larger than 10 cm who underwent isolated caudate lobe resection from January 2001 to December 2011 were retrospectively analyzed.
 Results: All the patients successfully completed the operation. There was no postoperative death. Median operative time was 288 min, and the estimated intraoperative blood loss was 2 260 mL. Postoperative morbidity rate was 44.4%. The patients were discharged successfully after active treatment. Overall survival rates at 1, 3, and 5 years were 80.2%, 52.1%, and 27.1%, respectively.
 Conclusion: Isolated caudate lobe resection is safe and effective for caudate lobe huge hepatocellular carcinoma.