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

Abstract	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.
Authors	Erbao Chen, Yuqian Mo, Jing Yi, Jie Liu, Ting Luo, Zheng Li, Zewei Lin, Yibing Hu, Zhilin Zou, Jikui Liu
Journal	Aging (Aging (Albany NY)) Vol. 15 Issue 16 Pg. 7933-7955 (08 16 2023) ISSN: 1945-4589 [Electronic] United States
PMID	37589508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Mechanistic Target of Rapamycin Complex 1 FABP5 protein, human Fatty Acid-Binding Proteins PAG1 protein, human Membrane Proteins Adaptor Proteins, Signal Transducing
Topics	Humans Carcinoma, Hepatocellular Liver Neoplasms Prognosis Carcinogenesis Immunotherapy Mechanistic Target of Rapamycin Complex 1 Fatty Acid-Binding Proteins Membrane Proteins Adaptor Proteins, Signal Transducing

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