The day will come to treat HCC in a drugstore?

Miura, Kouichi

doi:10.21037/hbsn.2017.07.09

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…A variety of cancer-related biomarkers can be found in tumor exosomes, including microRNAs (miRNAs), which may be used to detect BCa early. Exosome research has made some breakthroughs, but the speci c biological functions of exosomes remain unknown [7][8][9][10]. In this study, we investigated differentially-expressed exosome-related genes in BCa, and also conducted molecular clustering analysis based on TCGA datasets.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Shen,

Han,

Zhou

et al. 2023

Preprint

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Background Recent studies indicate exosomes play an important role in cell-to-cell communication, cancer metastasis, neovascularization, the regulation of the tumor immune microenvironment, and drug resistance in various tumors. However, the prognostic and therapeutic value of exosome-related genes in bladder cancer (BCa) remains to be determined. Hence, the goal of this study was to identify and validate a novel prognostic model based on exosome-associated genes for BCa patients Methods Differentially expressed exosome-related genes (DEGs) were analyzed using the Cancer Genome Atlas (TCGA) databases. DEGs closely associated with BCa patient survival prognosis were identified using Cox regression; and these genes are used for molecular typing. Moreover, we constructed a 17 multigene model using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The five external cohorts (i.e., GSE13507, GSE32894, GSE31684, GSE48075, and IMvigor210) of BCa patients were used to validate the accuracy by KM plot, ROC and calibration curves. Subsequently, we assessed immune infiltration using seven published algorithms: TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC. Furthermore, the correlation results between risk groups (scores) and overall survival, recognised immunoregolatory cells or common chemotherapeutic agents, clinicopathological data and immune checkpoint-related genes of BCa patients, were analyzed based on wilcox rank test, chi-square test, cox regression and spearman's correlation method. Additionally, we also preformed that the expression level of partial modeled genes was significantly associated with objective responses to anti-PD-1/PD-L1 treatment in the IMvigor210, GSE111636, GSE176307 or our Truce01 cohort. Results In BC patients, 156 exosome-related prognostic DEGs were identified, and were clustered into three classes. Subtypes C3 predicts worse OS, DSS, and PFS in patients with BCa. The prognostic model of 17 exosome-related genes showed good prediction performance by the TCGA training set, internal test set and five external verification sets. Our study also additionally confirmed that model riskscore was closely related with drug susceptibility, immune cell infiltration, and the prediction of immunotherapy efficacy. The high-risk group was characterized by a higher number of infiltrating macrophages M2 cells, and cancer-associated fibroblasts (CAFs). Lastly, we verified the protein and mRNA expression of six interested model-related genes (including AKR1B1, CGB5, CSPG4, P4HB, POLR3G and RAC3) from the Human Protein Atlas (HPA) and 10 paired BCa tissues collected by us. Conclusions In summary, the exosome-associated gene signature established by us exhibited a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, The model also might function as a chemotherapy and immune checkpoint inhibitor (ICI) treatment guidance.

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Section: Introductionmentioning

confidence: 99%

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Shen,

Han,

Zhou

et al. 2023

Preprint

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“…Exosomes derived from tumor tissue contain numerous cancer-related biomarkers, such as microRNAs (miRNAs), which can be used to detect HCC at an early stage. Although some breakthroughs have been made in the field of exosome research, the specific biological functions of exosomes have yet to be fully elucidated (12)(13)(14)(15). Therefore, the aim of this study was to comprehensively investigate exosome-related genes in HCC, which can help predict the outcome of HCC and discover potential new drug candidates for specific targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed liver exosome-related genes as candidate prognostic biomarkers for hepatocellular carcinoma

Zuo¹,

Kuai²,

Long³

et al. 2022

Ann Transl Med

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Background: Exosomes are involved in cell-to-cell communication, neovascularization, cancer metastasis, and drug resistance, which all play an important role in the occurrence and progression of hepatocellular carcinoma (HCC). Because there are few mechanistic studies about the function of exosomes in HCC, the goals of this study were to identify exosome-related genes in HCC, to establish a reliable prognostic model for HCC, and to explore underlying mechanisms. Methods: The exoRBase and The Cancer Genome Atlas (TCGA) databases were used to analyze differentially expressed genes (DEGs). Cox regression and least absolute shrinkage and selection operator analyses were used to identify DEGs closely related to the overall survival of patients with HCC. An exosome-related prognostic model was then constructed in TCGA and validated in the International Cancer Genome Consortium database. A nomogram was developed to predict survival. CIBERSORT was used to estimate the abundance of different types of immune cells. Immunotherapy-related DEGs were used to predict the effect of immunotherapy.Results: Forty-eight exosome-related DEGs were obtained; of them, five [exportin 1 (XPO1), lysosomal thiol reductase (IFI30), F-box protein 16 (FBXO16), calmodulin 1 (CALM1), MORC family CW-type zinc finger 3 (MORC3)] were selected to construct a predictive model. Patients with HCC were then divided into low-and high-risk groups using the best cut-off value, as determined by the X-tile software. Prognosis was significantly poorer in the high-risk than in the low-risk group (P=0.009; hazard ratio =2.65). Features related to exosomes were found to positively regulate immune response. Further analysis showed a higher risk score was associated with higher expression of immune checkpoint genes, including programmed death ligand 1 (PD-L1), programmed death ligand 1 (PD-L2), T cell Ig and ITIM domain (TIGIT), and indoleamine-2,3dioxygenase 1 (IDO1).Conclusions: This study has identified a novel signature based on exosome-related genes that has potential as a prognostic biomarker for HCC. Our research provides an immunological perspective for the development of precision treatment for HCC.

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“…Although some breakthroughs have been made in the eld of exosome, the speci c biological functions of exosome have not yet been fully elucidated. [9][10][11][12] Therefore, we are supposed to comprehensively study the exosome-related genes in HCC which may help to predict the outcome of HCC and nd potential new drug candidates for speci c targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed liver exosome-related genes as a candidate prognostic biomarker for hepatocellular carcinoma

Zuo¹,

Zhao²,

Bian³

et al. 2020

Preprint

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Background The function of exosome includes cell-to-cell communication, neovascularization, and metastasis of cancer cell and drug resistance, which plays an important part in the occurrence and progression of hepatocellular carcinoma (HCC). Because the mechanism in this area is less studied, our goal is to identify exosome-related genes in HCC, establish a reliable prognostic model for liver cancer patients, and explore its underlying mechanisms. Methods The exoRbase database and The Cancer Genome Atlas (TCGA) database were used to analyze differentially expressed genes (DEGs). Cox regression and LASSO analysis were applied to determine DEGs closely related to overall survival (OS). Then the exosome-related prognostic model was constructed in TCGA and validated in the database of International Cancer Genome Consortium (ICGC). Nomogram graph was performed to predict the survival. CIBERSORT was used to estimate the score of different type of immune cells. DEGs related to immunotherapy are used to predict the effect of immunotherapy. Results 48 exosome-related DEGs were obtained and five genes (XPO1, IFI30, FBXO16, CALM1, MORC3) among them were selected to construct predictive model. Then we divided the HCC patients into low-risk and high-risk groups by the best cut-off value according to the X-tile software. The high-risk related to exosome were significantly associated with a poor prognosis. Moreover, the features related to exosome could positively regulate immune response. At the same time, the proportion of T cell regulatory factors (Tregs) and macrophages M2 is higher in the high-risk group, and high-risk group exhibited higher expression of immune checkpoint molecular including PD-L1, PD-L2, TIGIT, and IDO1. Conclusions Overall, our research showed that markers related to exosomes were potential biomarkers for the prognosis of HCC, providing an immunological perspective for the development of precision treatment.

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The day will come to treat HCC in a drugstore?

Cited by 7 publications

References 16 publications

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Development and validation of a exosome-related gene signature for predicting prognosis, immune infiltration and immunotherapeutic response in bladder cancer

Differentially expressed liver exosome-related genes as candidate prognostic biomarkers for hepatocellular carcinoma

Differentially expressed liver exosome-related genes as a candidate prognostic biomarker for hepatocellular carcinoma

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