Elevated Expressions of Survivin and Endoglin in Patients with Hepatic Carcinoma

Chen, Wen‐Mei; Dong, Wenjing; Wang, Jintai; Wen, Zirong; Hao, Xinjie

doi:10.1089/cbr.2018.2539

Cited by 6 publications

(4 citation statements)

References 18 publications

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“…Ambrosini et al first described this gene as an oncogene that is prominently expressed in all common human cancers of the lung, colon, pancreas, prostate, and breast [39]. Consistent with the results of previous studies, Chen et al recently found that increased BIRC5 expressions are associated with histological grade, tumor size, and TNM stage in HCC patients which is consistent with our findings [40].…”

Section: Discussionsupporting

confidence: 93%

Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma

Qin

Zhang

Gong

et al. 2021

BioMed Research International

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Background. Accumulating studies have demonstrated that autophagy plays an important role in hepatocellular carcinoma (HCC). We aimed to construct a prognostic model based on autophagy-related genes (ARGs) to predict the survival of HCC patients. Methods. Differentially expressed ARGs were identified based on the expression data from The Cancer Genome Atlas and ARGs of the Human Autophagy Database. Univariate Cox regression analysis was used to identify the prognosis-related ARGs. Multivariate Cox regression analysis was performed to construct the prognostic model. Receiver operating characteristic (ROC), Kaplan-Meier curve, and multivariate Cox regression analyses were performed to test the prognostic value of the model. The prognostic value of the model was further confirmed by an independent data cohort obtained from the International Cancer Genome Consortium (ICGC) database. Results. A total of 34 prognosis-related ARGs were selected from 62 differentially expressed ARGs identified in HCC compared with noncancer tissues. After analysis, a novel prognostic model based on ARGs (PRKCD, BIRC5, and ATIC) was constructed. The risk score divided patients into high- or low-risk groups, which had significantly different survival rates. Multivariate Cox analysis indicated that the risk score was an independent risk factor for survival of HCC after adjusting for other conventional clinical parameters. ROC analysis showed that the predictive value of this model was better than that of other conventional clinical parameters. Moreover, the prognostic value of the model was further confirmed in an independent cohort from ICGC patients. Conclusion. The prognosis-related ARGs could provide new perspectives on HCC, and the model should be helpful for predicting the prognosis of HCC patients.

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Section: Discussionsupporting

confidence: 93%

Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma

Qin

Zhang

Gong

et al. 2021

BioMed Research International

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“…Studies have shown that BIRC5 is highly expressed in the vast majority of tumors, including HCC (Su, 2016). In addition, elevated BIRC5 levels have been found to be associated with histological grade, tumor size, and TNM stage in HCC patients (Chen et al, 2019). DLGAP5, also known as HURP, is a cell cycle regulatory gene that has been found to be highly expressed in liver cancer (Chang, Lin & Yeh, 2011; Tsou et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis

Feng²,

Hong

et al. 2019

PeerJ

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Hepatocellular carcinoma (HCC) is a common yet deadly form of malignant cancer. However, the specific mechanisms involved in HCC diagnosis have not yet fully elucidated. Herein, we screened four publically available Gene Expression Omnibus (GEO) expression profiles (GSE14520, GSE29721, GSE45267 and GSE60502), and used them to identify 409 differentially expressed genes (DEGs), including 142 and 267 up- and down-regulated genes, respectively. The DAVID database was used to look for functionally enriched pathways among DEGs, and the STRING database and Cytoscape platform were used to generate a protein-protein interaction (PPI) network for these DEGs. The cytoHubba plug-in was utilized to detect 185 hub genes, and three key clustering modules were constructed with the MCODE plug-in. Gene functional enrichment analyses of these three key clustering modules were further performed, and nine core genes including BIRC5, DLGAP5, DTL, FEN1, KIAA0101, KIF4A, MCM2, MKI67, and RFC4, were identified in the most critical cluster. Subsequently, the hierarchical clustering and expression of core genes in TCGA liver cancer tissues were analyzed using the UCSC Cancer Genomics Browser, and whether elevated core gene expression was linked to a poor prognosis in HCC patients was assessed using the GEPIA database. The PPI of the nine core genes revealed an interaction between FEN1, MCM2, RFC4, and BIRC5. Furthermore, the expression of FEN1 was positively correlated with that of three other core genes in TCGA liver cancer tissues. FEN1 expression in HCC and other tumor types was assessed with the FIREBROWSE and ONCOMINE databases, and results were verified in HCC samples and hepatoma cells. FEN1 levels were also positively correlated with tumor size, distant metastasis and vascular invasion. In conclusion, we identified nine core genes associated with HCC development, offering novel insight into HCC progression. In particular, the aberrantly elevated FEN1 may represent a potential biomarker for HCC diagnosis and treatment.

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“…37 Remarkably, endoglin is recently identified to be significantly involved in the development and progression of hepatocellular carcinoma and is widely used to target antiangiogenic therapy in many solid cancers. 38,39 Our previous study generated an aptamer hEnd-Apt that specifically binds human endoglin based on a SELEX approach. 40 Here, we developed a new therapeutic liposomal biomaterial by conjugating nanoliposomes with hEnd-Apt and an anti-CD3 antibody to allow faster encounter between T cells and tumors, with the purpose to render efficient tumor elimination.…”

Section: Introductionmentioning

confidence: 99%

Endoglin-Aptamer-Functionalized Liposome-Equipped PD-1-Silenced T Cells Enhance Antitumoral Immunotherapeutic Effects

Xie¹,

Hou²,

Yang³

et al. 2021

IJN

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Background:The broader application of adoptive cell therapy (ACT) in cancer immunotherapies (particularly for solid tumors) has always been limited by the immunosuppressive tumor microenvironment (TME) and the insufficient targetability of effector T cells, resulting in unsatisfied therapeutic outcome. Here, we designed a new strategy by using aptamer-based immunoliposomes to modify PD-1-silencing T cells, which were activated by dendritic cell (DC)/tumor fusion cells (FCs) to improve the antitumor potency of cytotoxic T lymphocytes (CTLs/CD8 + T cells). Methods: PD-1 gene was knocked out from CD8 + T cells using CRISPR/Cas9 system to liberate T cell activity from immunosuppression. The PD-1 − T cells were stimulated with DC/tumor FCs, followed by further functional modification of tumor-specific nanoliposomes (hEnd-Apt/CD3-Lipo) to generate FC/PD-1 − CTLs. The activation and proliferation and specificity of the modified FC/PD-1 − CTLs were measured. The antitumor activity of these CTLs against HepG2-tumors was evaluated in xenograft NOD/SCID mice, and the antitumor mechanism was investigated based on tissue immunohistochemistry and serum ELISA. Results: Our results indicated that the modification of hEnd-Apt/CD3-Lipo nanocomposites on the FC/PD-1 − CTLs had a more substantial synergetic effect in inhibiting tumor growth and prolonging animal survival, rather than other control liposomes. Furthermore, the hEnd-Apt/CD3-Lipo-modified FC/PD-1 − CTLs showed a stronger antitumor outcome in the tumorbearing mouse model, through the mechanisms of suppressing tumor cell proliferation, promoting tumor apoptosis, reducing angiogenesis but increasing the infiltration of the FC/ PD-1 − CTLs in the tumor tissue, as well as upregulating the systemic levels of IFN-γ, IL-2, TNF-α and IL-6 cytokines, by comparison of the control settings. Conclusion:In sum, our investigation suggests an enhancement of antitumor effect by the surface modification of endoglin-targeting nanoliposomes upon DC/tumor FC-activated PD-1 − CTLs, therefore, provides a new tumoral endoglin-targeted approach as a promising strategy to reduce immunosuppression of tumor microenvironment and improve the immunotherapeutic outcome of anticancer ACT.

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Elevated Expressions of Survivin and Endoglin in Patients with Hepatic Carcinoma

Cited by 6 publications

References 18 publications

Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma

Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma

Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis

Endoglin-Aptamer-Functionalized Liposome-Equipped PD-1-Silenced T Cells Enhance Antitumoral Immunotherapeutic Effects

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