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Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma.

ABSTRACT: Cytokinesis, the final step of mitosis, is critical for maintaining the ploidy level of cells. Cytokinesis is a complex, highly regulated process and its failure can lead to genetic instability and apoptosis, contributing to the development of cancer. Human hepatocellular carcinoma is often accompanied by a high frequency of aneuploidy and the DNA ploidy pattern observed in human hepatocellular carcinoma results mostly from impairments in cytokinesis. Many key regulators of cytokinesis are abnormally expressed in human hepatocellular carcinoma, and their expression levels are often correlated with patient prognosis. Moreover, preclinical studies have demonstrated that the inhibition of key cytokinesis regulators can suppress the growth of human hepatocellular carcinoma. Here, we provide an overview of the current understanding of the signaling networks regulating cytokinesis, the key cytokinesis regulators involved in the initiation and development of human hepatocellular carcinoma, and their applications as potential diagnostic and therapeutic biomarkers.

SUBMITTER: Qiao Y

PROVIDER: S-EPMC8243214 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma.

Qiao Yiting Y Pei Yunxin Y Luo Miao M Rajasekaran Muthukumar M Hui Kam M KM Chen Jianxiang J

Experimental biology and medicine (Maywood, N.J.) 20210425 12

Cytokinesis, the final step of mitosis, is critical for maintaining the ploidy level of cells. Cytokinesis is a complex, highly regulated process and its failure can lead to genetic instability and apoptosis, contributing to the development of cancer. Human hepatocellular carcinoma is often accompanied by a high frequency of aneuploidy and the DNA ploidy pattern observed in human hepatocellular carcinoma results mostly from impairments in cytokinesis. Many key regulators of cytokinesis are abnor ...[more]

PMID: 33899543

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Project description:Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.

Project description:BackgroundSeveral studies have indicated that CXC chemokines influence the prognosis and therapy in patients with hepatocellular carcinoma (HCC). However, there are limited studies on the roles of CXC chemokines in HCC based on data acquired from various databases. This study aimed to conduct an in-depth and comprehensive bioinformatic analysis of the expression and functions of CXC chemokines in HCC.MethodsData was obtained from various databases including ONCOMINE, UALCAN, STRING, GeneMinia, DAVID, Kaplan-Meier plotter, TIMER, GSCALite and NetworkAnalyst for the analysis of the expression and functions of the CXC chemokines in HCC.ResultsAnalysis of the differential expression levels of CXC chemokines between HCC and adjacent normal tissues revealed that the mRNA expression levels of CXCL1/2/5/6/7/12/14 were significantly lower in HCC tissues than those in adjacent normal tissues, whereas the mRNA expression levels of CXCL9/16/17 were significantly higher in HCC tissues. Analysis of the relationship between CXC chemokines and overall survival revealed that high mRNA expression levels of CXCL1/3/5/6/8 were associated with poor overall survival, whereas high mRNA expression levels of CXCL2/4/7/9/10/12 were associated with better overall survival. The functions of CXC chemokines and related genes were associated with cytokine-cytokine receptor interactions and chemokine signaling pathway. Analysis of the association between CXC chemokines and activity of cancer pathways indicated that the DNA damage response and hormone androgen receptor (AR) signaling pathways were inhibited, whereas apoptosis, epithelial-mesenchymal transition (EMT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways were activated. The expression of CXC chemokines was positively correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells).ConclusionsThis study has demonstrated that CXC chemokines can influence survival of patients with HCC by recruiting different types of immune cells into the tumor microenvironment.

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Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma.

Publications

Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma.

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