High expression of PDZ-binding kinase is correlated with poor prognosis and immune infiltrates in hepatocellular carcinoma

Mu, Wei; Xie, Yaoli; Li, Jinhu; Yan, Runzhi; Zhang, Jingxian; Liu, Yue; Fan, Yimin

doi:10.1186/s12957-021-02479-w

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…Additionally, there might be some biases in the indication of preoperative supplemental treatment; this depends on the surgeons’ decision and the strategies of TAE followed by the radiologists. Furthermore, advanced HCC has various statuses to be discussed other than tumor size, such as lymph node metastasis [ 27 ], and clinical application of biomarker research to clarify the oncological characteristics of HCC is also a future issue [ 28 ]. Nevertheless, the results of this study are suggestive of the oncological effectiveness of the intended preoperative TAE for patients with a large HCC.…”

Section: Discussionmentioning

confidence: 99%

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

et al. 2022

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Background Generally, a large tumor size of hepatocellular carcinoma (HCC) is associated with poor visibility and uncertainty in the surgical field which results in increased surgical difficulty as well as unfavorable postoperative outcomes. We performed intended preoperative trans-arterial embolization (TAE) in patients with a large HCC. In this study, we investigated the oncological significance of intended preoperative TAE for a large HCC, using a comparison between patients with and without TAE, and detailed analyses for pre- and post-TAE status. Methods A total of 411 patients who underwent hepatectomy for primary HCC at the University of Yamanashi Hospital between January 2007 and December 2018 were included in this study. The patients were divided into two groups: patients with larger HCCs (≥50 mm, n=51) and those with smaller HCC (<50 mm, n=360) according to the size of their HCCs. Comparison of clinicopathological features between these groups and clinical outcomes between the TAE and non-TAE groups were compared. In addition, a detailed analysis of each case in the TAE group was conducted, comparing clinicopathological factors between pre- and post-TAE status. Results The clinical unfavorable short- and long-term outcomes of patients with large HCCs (≥50 mm) were revealed compared to those with small HCCs (<50 mm). The prognostic analyses showed that a large tumor size and increased tumor markers, multiple tumor numbers, and others were adverse prognostic factors, and vascular invasions and residual tumors were included in the multivariate analysis. Further detailed analyses revealed that the average rates of change in tumor size and tumor shrinkage after TAE were − 48.6±35.6 mm and − 30.7±17.0%, respectively. Pathological high necrotic changes in the tumor, after multiple-times TAE aiming to a better effect, were related to a better prognosis in patients with large HCC. Poor prognostic factors became less common in patients who underwent intended preoperative TAE, and these patients had better prognoses. Conclusions The large tumor size of HCC is associated with unfavorable outcomes; the intended preoperative TAE for large HCC patients performed multiple times aiming to affect the tumor as much as possible might improve their prognoses.

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Section: Discussionmentioning

confidence: 99%

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

et al. 2022

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“…HCC comprises 75-85% of liver cancers and has a poor prognosis [1]. Some studies have shown multiple genes present good predictive potential in assessing HCC prognosis [15][16][17][18]. Recently, the importance of ICI therapy in HCC patients has been proven.…”

Section: Discussionmentioning

confidence: 99%

“…Generally speaking, a model with more genes and gene pairs will attain a higher AUC of OS. Second, our model did not include some earlier reported HCC prognosis genes [15][16][17][18]. Our prediction model only included 3 immune-related gene pairs with 6 genes to assess both the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients, and it was hard to include all genes reported.…”

Section: Table 2 the Chi-square Test Of The Relation Between Risk Sco...mentioning

confidence: 99%

Risk predictive model based on three immune-related gene pairs to assess prognosis and therapeutic sensitivity for hepatocellular carcinoma

et al. 2022

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Background Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients. Methods The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients. Results A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis. Conclusions Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.

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“…CMap ( https://clue.io/ ) [ 26 – 28 ] can be utilized to discover the mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The CMap database was updated with the top 50 EZH2-related up- and down-regulated genes from The Linked Omics database in order to predict potential drug targets for LUAD.…”

Section: Methodsmentioning

confidence: 99%

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

Fan¹,

Zhang²,

Han

et al. 2023

BMC Bioinformatics

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Backgrounds It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. Methods The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan–Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. Results In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. Conclusions Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

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High expression of PDZ-binding kinase is correlated with poor prognosis and immune infiltrates in hepatocellular carcinoma

Cited by 10 publications

References 51 publications

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

Risk predictive model based on three immune-related gene pairs to assess prognosis and therapeutic sensitivity for hepatocellular carcinoma

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

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