Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Autophagy and biotransformation affect sorafenib resistance in hepatocellular carcinoma.

As sorafenib is a first-line drug for treating advanced hepatocellular carcinoma, sorafenib resistance has historically attracted attention. However, most of this attention has been focused on a series of mechanisms related to drug resistance arising after sorafenib treatment. In this study, we used proteomic techniques to explore the potential mechanisms by which pretreatment factors affect sorafenib resistance. The degree of redundant pathway PI3K/AKT activation, biotransformation capacity, and autophagy level in hepatocellular carcinoma patients prior to sorafenib treatment might affect their sensitivity to sorafenib, in which ADH1A and STING1 are key molecules. These three factors could interact mechanistically to promote tumor cell survival, might be malignant features of tumor cells, and are associated with hepatocellular carcinoma prognosis. Our study suggests possible avenues of therapeutic intervention for patients with sorafenib-resistance and the potential application of immunotherapy with the aim of improving the survival of such patients.

Elevated FOXA1 Expression Indicates Poor Prognosis in Liver Cancer due to Its Effects on Cell Proliferation and Metastasis.

Purpose: Studying the pathogenesis of liver cancer is conducive to the exploration of effective diagnostic and prognostic biomarkers. In this study, we investigated the expression of FOXA1 and its oncogenic role in hepatocellular carcinoma (HCC). Methods: Transcriptome data of HCC tissues were downloaded from The Cancer Genome Atlas (TCGA) and GEO databases and analyzed using R software. We also upregulated FOXA1 expression in HCC cells and investigated the role of FOXA1 in the proliferation and migration of HCC cells through proliferation, colony formation, wound healing, and Transwell assays. Results: An analysis of the transcriptome data in TCGA database revealed found that FOXA1 is highly expressed in HCC tissues and that patients with low FOXA1 expression have a better prognosis. High FOXA1 expression was mainly associated with extracellular matrix organization, cancer, and mitosis. The results of an immunohistochemistry (IHC) assay showed that FOXA1 protein was highly expressed in HCC tissues, and patients with low FOXA1 expression showed longer disease-specific survival times and progression-free intervals. The results from quantitative reverse transcription-PCR (RT-qPCR) and Western blot experiments showed that the expression of FOXA1 in liver cancer cell lines was higher than that in immortalized human liver cell lines. Proliferation, wound healing, and Transwell experiments showed that FOXA1 enhanced the proliferation and migration abilities of liver cancer and immortalized human cell lines. Conclusion: Our research suggests that FOXA1 plays an important role in promoting the recurrence and metastasis of HCC by increasing cell proliferation and metastasis.

Integrated analysis of the rhesus monkey liver transcriptome during development and human primary HCC AFP-related gene expression.

Embryonic development and tumorigenesis have a certain degree of similarity. Alpha-fetoprotein (AFP), a protein related to embryonic development, is a well-known biomarker for the diagnosis and prognosis of hepatocellular carcinoma (HCC). In this study, we analyzed the differences in gene expression profiles and molecular mechanisms in human HCC tissues from patients in AFPhigh (serum AFP level ≥ 25 ng/mL) and AFPlow (serum AFP level < 25 ng/mL) groups. The results indicated that AFPhigh HCC has more malignant biological characteristics. Single-sample gene set enrichment analysis (ssGSEA) showed significantly higher levels of genes expressed in dendritic cells, neutrophils, and natural killer cells in the AFPlow group than in the AFPhigh group. Then, we defined a rhesus monkey fetal liver developmental landscape and compared it to the HCC gene expression profile. The gene signatures of AFPhigh HCC tissues were similar to those of early embryonic liver tissues. In this study, we comprehensively analyzed the rhesus monkey liver transcriptome during development and human primary HCC AFP-related gene expression profiles and clarified the function of AFP in the occurrence and development of HCC from the perspective of developmental biology, which might provide a new perspective on the pathogenesis of HCC.