Six Novel Biomarkers for Diagnosis and Prognosis of Esophageal squamous cell carcinoma: validated by scRNA-seq and qPCR

Zheng, Liuhai; Li, Linzhi; Xie, Jun; Jin, Hai; Zhu, Nianyong

doi:10.7150/jca.50443

Cited by 42 publications

(33 citation statements)

References 49 publications

(51 reference statements)

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“…PBK/TOPK is a potential target for antitumor therapy. First, based on the distribution of its expression, PBK/TOPK is rarely expressed in normal tissues, as its expression is detected only in testicular and embryonic tissues but is expressed at high levels in some malignancies; its expression level is negatively correlated with patient prognosis [3][4][5]. Second, regarding the molecular mechanism, PBK/TOPK, a mitotic kinase is involved in regulating multiple important signaling pathways such as p53 [6], MAPK [3], and PI3K/AKT [7], playing an important role in the process of tumorigenesis and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, several recent studies have suggested that PBK/TOPK may be associated with tumor-infiltrating immune cells and have a potential target for cancer immunotherapy [5,11,12]. is study is the first to conduct a pancancer analysis of PBK/TOPK using Oncomine, Human Protein Atlas(HPA), ULCAN, the Tumor Immune Estimation Resource 2.0 (TIMER2.0), STRING, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the data collected from e Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx).…”

Section: Introductionmentioning

confidence: 99%

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PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

Feng

Zhang

Ling

et al. 2021

Journal of Oncology

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Background. PDZ binding kinase (PBK)/T-LAK cell-derived protein kinase (TOPK) is an important mitotic kinase that promotes tumor progression in some cancers. However, the pan-cancer analysis of PBK/TOPK and its role in tumor immunity are limited. Methods. The oncogenic and immune roles of PBK in various cancers were explored using multiple databases, including Oncomine, Human Protein Atlas, ULCAN, Tumor Immune Estimation Resource 2.0, STRING, and Gene Expression Profiling Interactive Analysis 2, and data collected from The Cancer Genome Atlas and Genotype-Tissue Expression Project. Several bioinformatics tools and methods were used for quantitative analyses and panoramic descriptions, such as the DESeq2 and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results. PBK was expressed at higher levels in most solid tumors than in normal tissues in multiple databases. PBK was associated with an advanced tumor stage and grade and a poor prognosis in most cases. PBK was associated with tumor immune cell infiltration in most cases and was especially positively correlated with TAMs, Tregs, MDSCs, and T cell exhaustion in KIRC, LGG, and LIHC. PBK was closely related to TMB, MSI, and immune checkpoint genes in various cancers, and patients with higher expression of PBK in KIRC, LGG, and LIHC had higher TIDE scores and lower immune responses in the predicted results. PBK was closely related to cell cycle regulation and immune-related processes in LIHC and LGG according to GO and KEGG enrichment analyses. Conclusions. PBK may play an oncogenic role in most solid tumors and promotes immune escape, especially in KIRC, LGG, and LIHC. This study suggests the potential value of PBK inhibitors combined with immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

Feng

Zhang

Ling

et al. 2021

Journal of Oncology

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“…KIF 11 is essential for spheroid formation of ESCA cells [ 34 ]. ScRNA-seq and qPCR analysis uncovered that KIF 20 A possesses the potential to diagnose and predict ESCA patients' prognosis [ 35 ]. For TOP 2 A , experimental data demonstrate that it can affect the resistance of ESCA cells to paclitaxel [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Correlation Network Analysis Identifies Specific Functional Modules and Genes in Esophageal Cancer

Wang

et al. 2021

Journal of Oncology

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Objective. Esophageal cancer (ESCA) is one of the most aggressive malignancies globally with an undesirable five-year survival rate. Here, this study was conducted for determining specific functional genes linked with ESCA initiation and progression. Methods. Gene expression profiling of ESCA was curated from TCGA (containing 160 ESCA and 11 nontumor specimens) and GSE38129 (30 paired ESCA and nontumor tissues) datasets. Differential expression analysis was conducted between ESCA and nontumor tissues with adjusted p value <0.05 and |log2fold-change|>1. Weighted gene coexpression network analysis (WGCNA) was conducted for determining the ESCA-specific coexpression modules and genes. Thereafter, ESCA-specific differentially expressed genes (DEGs) were intersected. Functional enrichment analysis was then presented with clusterProfiler package. Protein-protein interaction was conducted, and hub genes were determined. Association of hub genes with pathological staging was evaluated, and survival analysis was presented among ESCA patients. Results. This study determined 91 ESCA-specific DEGs following intersection of DEGs and ESCA-specific genes in TCGA and GSE38129 datasets. They were remarkably linked to cell cycle progression and carcinogenic pathways like the p53 signaling pathway, cellular senescence, and apoptosis. Ten ESCA-specific hub genes were determined, containing ASPM, BUB1B, CCNA2, CDC20, CDK1, DLGAP5, KIF11, KIF20 A, TOP2A, and TPX2. They were prominently associated with pathological staging. Among them, KIF11 upregulation was in relation to undesirable prognosis of ESCA patients. Conclusion. Collectively, we determined ESCA-specific coexpression modules and hub genes, which offered the foundation for future research concerning the mechanistic basis of ESCA.

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“…Many studies about the possible role of PBK in tumor immune cell in ltration have emerged in recent years. In Esophageal squamous cell carcinoma, immune in ltration analysis showed that in ltration of dendritic cells was signi cantly negatively correlated with PBK expression levels [44]. Zhou et al investigated the immune microenvironment in Ewing's sarcoma patients to identify immune-related gene signatures.…”

Section: Discussionmentioning

confidence: 99%

High Expression of PDZ-binding Kinase Is Correlated With Poor Prognosis and Immune Infiltrates in Hepatocellular Cacinoma

Xie

et al. 2021

Preprint

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BackgroundPDZ-binding kinase (PBK) encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. There is evidence that overexpression of this gene is associated with tumorigenesis. However, the role of PBK in hepatocellular carcinoma (HCC) remain unclear. Therefore, we evaluated the prognostic role of PBK and its correlation with immune infiltrates in Hepatocellular Carcinoma.MethodsThe expression of PBK in pan-cancers was studied by Onconmine and TIMER. The expression of PBK in HCC patients and its relationship with clinicopathological characteristics were analyzed using The Gene Expression Profiling Interactive Analysis (GEPIA), The human protein atlas database (HPA), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of PBK in HCC patients. The relationship between PBK and prognosis of HCC was performed by GEPIA and Kaplan Meier plotter web tool. The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients. LinkedOmics was applied to investigate co-expression associated with PBK and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The network map of PBK and related genes is constructed by GeneMANIA. Finally, TIMER and TISIDB were used to analyze the correlations between PBK and tumor-infiltrating immune cells.ResultsPBK was highly expressed in many types of tumors, including hepatocellular carcinoma, and was significantly related to tumor stage (P=0.0089), age (P=0.0131) and race (P=0.0024) of HCC patients. The receiver operating characteristic (ROC) curve analysis from 4 GEO databases showed that PBK is a predictive marker for HCC. Moreover, high expression of PBK correlated with poor prognosis. Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062-2.311, P= 0.024). The Protein–protein interaction network showed that PBK significantly interacted with LRRC47, ARAF, LGALS9B, TTK, MELK and other essential genes. Furthermore, enrichment analysis showed that PBK and co-expressed genes participated in many biological processes, cell composition, molecular functions and pathways in HCC. Finally, the immune infiltration analysis by TIMER and TISIDB indicated that PBK expression tightly correlated with the infiltration of tumor-infiltrating lymphocytes (TILs), chemokines, and receptors.ConclusionsHigh expression of PBK is significantly correlated with poor survival and immune infiltrates in hepatocellular carcinoma. Our study suggests that PBK can be used as a biomarker of poor prognosis and potential immune therapy target in hepatocellular carcinoma.

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Six Novel Biomarkers for Diagnosis and Prognosis of Esophageal squamous cell carcinoma: validated by scRNA-seq and qPCR

Cited by 42 publications

References 49 publications

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

Weighted Gene Correlation Network Analysis Identifies Specific Functional Modules and Genes in Esophageal Cancer

High Expression of PDZ-binding Kinase Is Correlated With Poor Prognosis and Immune Infiltrates in Hepatocellular Cacinoma

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