Editor’s Note: In an effort to keep clinicians and researchers in the field of hepatology abreast of the latest academic knowledge and research trends, ” Hepatology Digest ” has collaborated with the “Journal of Clinical and Translational Hepatology” (JCTH) to introduce the “Journal Co-Read” section. Each week, this section selects and interprets highlights from a key publication, summarizing its main points in the hope of enhancing clinical diagnostic and treatment levels, inspiring research thinking, and improving writing skills.
Gene prediction models have recently achieved notable success in the early diagnosis of hepatocellular carcinoma (HCC). A 2023 publication in JCTH, titled “Establishment and Validation of a Four Stress Granule-Related Gene Signature in Hepatocellular Carcinoma,” has revealed the role and corresponding mechanisms of stress granule-related genes in the prognosis of HCC. This suggests that stress granules could be a promising target for prognosis and cancer treatment[1].
Key Excerpts:
**Stress Granules (SGs): These are non-membrane-bound molecular aggregates in the cytoplasm, mainly composed of mRNA, RNA-binding proteins, and ribosomal subunits. In eukaryotic cells, under adverse external conditions like hypoxia, acidosis, oxidative stress, or viral infections, SGs can enhance cell survival by regulating protein synthesis. In tumor cells, SGs similarly enhance survival under such conditions. Thus, SGs are increasingly seen as a target for cancer treatment. The core protein G3BP1 for SGs formation, highly expressed in various cancers including prostate, lung, and breast cancers, promotes tumor migration and proliferation.
**Hepatocellular Carcinoma (HCC): As the most common primary liver cancer, HCC often remains undetected until advanced stages. Early diagnosis is crucial for effective treatment. Traditional prognostic models, relying on histological typing and cancer staging, are less effective for early-stage HCC prognosis. The study explores the role and mechanisms of stress granule genes (SGGs) in HCC prognosis.
Research Highlights:
**Study Process (Figure 1): The study first analyzed 463 SGGs in the TCGA-HCC database using bioinformatics, identifying 34 differentially expressed SGGs in liver cancer, with 33 being highly expressed. A gene signature comprising KPNA2, MEX3A, WDR62, and SFN was developed through regression and survival analysis, effectively predicting patient survival. These genes were found highly expressed in human liver cancer tissues and various liver cancer cell lines. Knocking down these SGGs reduced tumor cell proliferation and migration. Furthermore, knocking down any of these genes affected SG formation, possibly due to reduced G3BP1 mRNA levels. Isolating G3BP1, known to inhibit tumor progression by inhibiting SG formation, corroborates these findings.
**Conclusion: This study established and validated a liver cancer prognostic model based on four SGGs, revealing their potential mechanisms in regulating SGs and affecting HCC progression. SGs, formed in response to adverse factors and linked to several diseases including cancer, coordinate various oncogenic signals and external stimuli to mediate cancer cell proliferation, invasion, and metastasis. SGs are thus a promising target for prognosis and cancer treatment. Although many SG-related proteins have been identified, their role as markers for clinical outcomes in HCC patients has not been explored. Since most SGGs are upregulated and associated with poor HCC prognosis, researching SGG-based approaches as independent prognostic tools for accurately predicting HCC prognosis is intriguing.
Reference:
[1] Li M, Fan X, Zhao J, et al. Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma. J Clin Transl Hepatol 2023. doi: 10.14218/JCTH.2023.00019. [Link](https://www.xiahepublishing.com/2310-8819/JCTH-2023-00019)
Team Introduction:
**Corresponding Author:
Dr. Jiajun Zhao: an expert on the strategic advisory committee for the 2030 Science and Technology Innovation Project, focusing on cancer, cardiovascular, respiratory, and metabolic disease prevention and research. He is a recipient of the National Innovation Pioneer Award, Wu Yang Award, and the first National Distinguished Physician award. He is the chairman of the Endocrinology Branch of the Chinese Medical Association, specializing in endocrinology and metabolism research.
Dr. Dawei Wang: Associate researcher at Shandong First Medical University and Affiliated Provincial Hospital, focusing on gene editing, vesicle transport mechanisms, and targeted drug research.
**Lead Author:
Dr. Li Mengzhu, a graduate student at Shandong University, specializes in endocrinology and metabolic research.
Journal Introduction:
**Journal of Clinical and Translational Hepatology (JCTH): An English-language academic journal published by Xia & He Publishing Inc., sponsored by the Second Affiliated Hospital of Chongqing Medical University. It primarily publishes clinical or translational research papers, reviews, and commentaries in the field of liver diseases.
– 2022 Impact Factor: 3.6
– 2022 CiteScore: 5.6
– Submissions: [Link](https://mc03.manuscriptcentral.com/jcth)
– Contact: jcth@xiahepublishing.com (Teacher Chen)
TAG: review; Stress Granules (SGs); Hepatocellular Carcinoma
