Molecular subtype identification and signature construction based on Golgi apparatus-related genes for better prediction prognosis and immunotherapy response in hepatocellular carcinoma
Open accessAbstract
Introduction: The Golgi apparatus (GA) is the center of protein and lipid synthesis and modification in normal cells and is involved in regulating various cellular process as a signaling hub, the dysfunction of which can lead to the development of various pathological conditions, including tumors. Mutations in Golgi apparatus-related genes (GARGs) are prevalent in most tumors, and their mutations can make them pro-tumor metastatic. The aim of this study was to analyze the predictive role of GARGs in the prognosis and immunotherapeutic outcome of hepatocellular carcinoma. Methods: We used TCGA, GEO and ICGC databases to classify hepatocellular carcinoma samples into two molecular subtypes based on the expression of GARGs. Signature construction was then performed using GARGs, and signature genes were selected for expression validation and tumor phenotype experiments to determine the role of GARGs in the prognosis of hepatocellular carcinoma. Results: Using the TCGA, GEO and ICGC databases, two major subtypes of molecular heterogeneity among hepatocellular carcinoma tumors were identified based on the expression of GARGs, C1 as a high-risk subtype (low survival) and C2 as a low-risk subtype (high survival). The high-risk subtype had lower StromalScore, ImmuneScore, ESTIMATEScore and higher TumorPurity, indicating poorer treatment outcome for ICI. Meanwhile, we constructed a new risk assessment profile for hepatocellular carcinoma based on GARGs, and we found that the high-risk group had a worse prognosis, a higher risk of immune escape, and a higher TP53 mutation rate. Meanwhile, TME analysis showed higher tumor purity TumorPurity and lower ESTIMATEScore, ImmuneScore and StromalScore in the high-risk group. We also found that the high-risk group responded more strongly to a variety of anticancer drugs, which is useful for guiding clinical drug use. Meanwhile, the expression of BSG was experimentally found to be associated with poor prognosis of HCC. After interfering with the expression of BSG in HCC cells SMMC-7721, the proliferation and migration ability of HCC cells were significantly restricted. Discussion: The signature we constructed using GARGs can well predict the prognosis and immunotherapy effect of hepatocellular carcinoma, providing new ideas and strategies for the treatment of hepatocellular carcinoma.
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Bioinformatic analysis linked GDI1 to pathways such as KRAS and mTORC1 signaling.
“Bioinformatic analysis linked GDI1 to pathways such as KRAS and mTORC1 signaling [19]”
From Construction and validation of golgi apparatus-related genes as predictors of the immune microenvironment and prognosis in colorectal cancer (2026) · cites this paper as [19]
The Results section on differential expression and prognosis reports enrichment for glycosphingolipid biosynthesis and sphingolipid metabolism, but does not link GDI1 to KRAS or mTORC1 signaling. Searches of our copy for GDI1, KRAS, and mTORC1 found no passage addressing the claimed link; the paper’s pathway-analysis methods alone do not establish it. (LLM, conf=0.76)
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- Authors
- Sun, L., Liu, Z., Wu, Z., Ning, K., Hu, J., Chen, Z., Wu, Z., & Yin, X.
- Affiliations
- Second Affiliated Hospital of Nanchang University (CN)
- First Affiliated Hospital of Nanchang University (CN)
- Corresponding author
- Yin, Xiangbao
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2023-03-27
- Volume
- 14
- Pages
- 1113455-1113455
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC10083374
- OpenAlex
- W4360982620
- Cited by
- 14
- References
- 35
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 2 · 2023: 3
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hepatocellular carcinoma, molecular subtypes, prognostic signature, immunotherapy response, immune evasion, tumor microenvironment, immune checkpoint inhibitors, TP53 mutation, brewer's spent grain, drug response prediction, cell proliferation and migration
- MeSH terms
- Golgi Apparatus, Carcinoma, Hepatocellular, Humans, Immunotherapy, Liver Neoplasms, Prognosis
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