Research Paper Volume 15, Issue 16 pp 7933—7955

A novel hepatocellular carcinoma-specific mTORC1-related signature for anticipating prognosis and immunotherapy

Erbao Chen1, *, , Yuqian Mo2, *, , Jing Yi1, *, , Jie Liu1, , Ting Luo3, , Zheng Li4, , Zewei Lin1, , Yibing Hu5, , Zhilin Zou4, , Jikui Liu1, ,

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
  • 2 School of Public Health, Guangdong Medical University, Zhanjiang, Guangdong, China
  • 3 Operating Room, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
  • 4 Department of Ophthalmology, Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 5 Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
* Equal contribution and share first authorship

Received: November 19, 2022       Accepted: June 9, 2023       Published: August 16, 2023
How to Cite

Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Tumor oncogenesis, cancer metastasis, and immune evasion were substantially impacted by the mammalian target of the rapamycin complex 1 (mTORC1) pathway. However, in hepatocellular carcinoma (HCC), no mTORC1 signaling-based gene signature has ever been published. mTORC1 scores were computed employing a single sample gene set enrichment analysis based on databases including the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). The PAG1, LHFPL2, and FABP5 expression levels were obtained to construct a mTORC1 pathway-related model. In two databases, the overall survival (OS) rate was shorter for high-mTORC1 score patients compared to those with low scores. The activation of TFs in the group with high risk was enhanced, such as the HIF-1 pathway. Additionally, it was discovered that a high mTORC1 score was linked to an immune exclusion phenotype and enhanced immunosuppressive cell infiltration. Notably, it was discovered that high-mTORC1 scores patients had poorer immunotherapeutic results and might not gain benefit from immunotherapy. When compared to the low HCC metastatic cell lines, the high HCC metastatic cell lines have overexpressed levels of PAG1, LHFPL2, and FABP5 expression. The expression of PAG1, LHFPL2, and FABP5 was inhibited by the MAPK and mTORC1 pathway inhibitors. Our study identified mTORC1 score signature can aid in the development of individualized immunotherapy protocols and predict the HCC patients’ prognoses.


mTORC1: The mammalian target of the rapamycin complex 1; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; HCC: Hepatocellular carcinoma; LIHC: Liver hepatocellular carcinoma; OS: Overall survival; ROC: Receiver operating characteristic; HIF-1: hypoxia inducible factor-1; PAG1: Phosphoprotein associated with glycosphingolipid-enriched microdomains; LHFPL2: LHFPL tetraspan subfamily member 2; FABP5: Fatty acid binding protein 5; MAPK: Mitogen-activated protein kinase; PI3K: Phosphatidylinositol 3-kinase; VEGF: Vascular endothelial growth factor; DEG: Differentially expressed gene; GO: Gene ontology; KEGG: Enrichment and Kyoto Encyclopedia of Genes and Genomes; FDR: False discovery rate; GSEA: Gene set enrichment analysis; PCR: Polymerase chain reaction; TME: Tumor microenvironment; PD-1: Programmed death-1.