Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma

Ye, Jiazhou; Lin, Yan; Gao, Xing; Lu, Lu; Huang, Xi; Huang, Shilin; Bai, Tao; Wu, Guobin; Luo, Xi; Li, Yongqiang; Liang, Rong

doi:10.3390/cancers14225721

Cited by 5 publications

(2 citation statements)

References 61 publications

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“…These studies have performed differential gene analysis on liver cancer data from multiple datasets of the TCGA database and GEO. These studies have identified GNA14 as one of the key characteristic genes that affect the prognosis of liver cancer patients (Yu et al 2020a ; Ye et al 2022 ). Subsequent experiments have confirmed the discovery that GNA14 is a prognostic protective gene in patients with liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of Exosomes-Related Gene Risk Model in Hepatocellular Carcinoma

et al. 2023

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Hepatocellular carcinoma (HCC) is a challenging disease to evaluate in terms of prognosis, requiring close attention to the prognosis of HCC patients. Exosomes have been shown to play an important role in HCC development and have significant potential in managing HCC patient prognosis, as they are detectable in patients’ blood. By using small extracellular vesicular RNA, liquid biopsies can reflect the underlying physiological and pathological status of the originating cells, providing a valuable assessment of human health. No study has explored the diagnostic value of mRNA expression changes in exosomes for liver cancer. The present study investigated establishing a risk prognosis model based on mRNA expression levels in exosomes from blood samples of liver cancer patients and evaluated its diagnostic and prognostic value, providing new targets for liver cancer detection. We obtained mRNA data from HCC patients and normal controls from the TCGA and exoRBase 2.0 databases and established a risk prognostic assessment model using exosomes-related risk genes selected through prognostic analysis and Lasso Cox analysis. The patients were divided into high-risk and low-risk groups based on median risk score values to validate the independence and evaluability of the risk score. The clinical value of the model was further analyzed using a nomograph model, and the efficacy of immunotherapy and cell-origin types of prognostic risk genes were further assessed in the high- and low-risk groups by immune checkpoint and single-cell sequencing. A total of 44 genes were found to be significantly associated with the prognosis of HCC patients. From this group, we selected six genes (CLEC3B, CYP2C9, GNA14, NQO1, NT5DC2, and S100A9) as exosomal risk genes and used them as a basis for the risk prognosis model. The clinical information of HCC patients from the TCGA and ICGC databases demonstrated that the risk prognostic score of the model established in this study was an independent prognostic factor with good robustness. When pathological stage and risk prognostic score were incorporated into the model to predict clinical outcomes, the nomograph model had the best clinical benefit. Furthermore, immune checkpoint assays and single-cell sequencing analysis suggested that exosomal risk genes were derived from different cell types and that immunotherapy in the high-risk groups could be beneficial. Our study demonstrated that the prognostic scoring model based on exosomal mRNA was highly effective. The six genes selected using the scoring model have been previously reported to be associated with the occurrence and development of liver cancer. However, this study is the first to confirm that these related genes existed in the blood exosomes, which could be used for liquid biopsy of patients with liver cancer, thereby avoiding the need for puncture diagnosis. This approach has a high value in clinical application. Through single-cell sequencing, we found that the six genes in the risk model originate from multiple cell types. This finding suggests that the exosomal characteristic molecules secreted by different types of cells in the microenvironment of liver cancer may serve as diagnostic markers.

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Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of Exosomes-Related Gene Risk Model in Hepatocellular Carcinoma

et al. 2023

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“…We also identified several genes functioning in cell adhesion. GNA14, encoding a member of the guanine nucleotide binding, or G protein family, was a wellknown target in hepatocellular carcinoma and vascular tumors (85,86). The protein encoded by NLGN4Y (Neuroligin 4 Y-Linked) is presented at the postsynaptic side of the synapse (87).…”

Section: Genome-wide Crispr-cas9 Screening Of Arsenic Trioxide In Hap...mentioning

confidence: 99%

The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening

et al. 2023

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IntroductionArsenic trioxide (ATO) is a promising anticancer drug for hematological malignancy. Given the dramatic efficacy of acute promyelocytic leukemia (APL), ATO has been utilized in other types of cancers, including solid tumors. Unfortunately, the results were not comparable with the effects on APL, and the resistance mechanism has not been clarified yet. This study intends to identify relevant genes and pathways affecting ATO drug sensitivity through genome-wide CRISPR-Cas9 knockdown screening to provide a panoramic view for further study of ATO targets and improved clinical outcomes.MethodsA genome-wide CRISPR-Cas9 knockdown screening system was constructed for ATO screening. The screening results were processed with MAGeCK, and the results were subjected to pathway enrichment analysis using WebGestalt and KOBAS. We also performed protein-protein interaction (PPI) network analysis using String and Cytoscape, followed by expression profiling and survival curve analysis of critical genes. Virtual screening was used to recognize drugs that may interact with the hub gene.ResultsWe applied enrichment analysis and identified vital ATO-related pathways such as metabolism, chemokines and cytokines production and signaling, and immune system responses. In addition, we identified KEAP1 as the top gene relating to ATO resistance. We found that KEAP1 expression was higher in the pan-cancer, including ALL, than in normal tissue. Patients with acute myeloid leukemia (AML) with higher KEAP1 expression had worse overall survival (OS). A virtual screen showed that etoposide and eltrombopag could bind to KEAP1 and potentially interact with ATO.DiscussionATO is a multi-target anticancer drug, and the key pathways regulating its sensitivity include oxidative stress, metabolism, chemokines and cytokines, and the immune system. KEAP1 is the most critical gene regulating ATO drug sensitivity, which is related to AML prognosis and may bind to some clinical drugs leading to an interaction with ATO. These integrated results provided new insights into the pharmacological mechanism of ATO and potentiate for further applications in cancer treatments.

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IGFALS suppresses hepatocellular carcinoma progression by stabilizing PPAR-γ

Xu,

Xiong,

Chen

et al. 2024

International Immunopharmacology

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Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma

Cited by 5 publications

References 61 publications

Establishment and Evaluation of Exosomes-Related Gene Risk Model in Hepatocellular Carcinoma

Establishment and Evaluation of Exosomes-Related Gene Risk Model in Hepatocellular Carcinoma

The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening

IGFALS suppresses hepatocellular carcinoma progression by stabilizing PPAR-γ

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