Prognostic value of CLIC3 mRNA overexpression in bladder cancer

Chen, Mei; Zhang, Shufang; Wen, Xiaohong; Cao, Hui; Gao, Yuanhui

doi:10.7717/peerj.8348

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…The informed consent of the patients and the approval of the ethics committee of Haikou Hospital, affiliated to Xiangya Medical College of Central South University were obtained before specimen collection. The operation steps and calculation methods of quantitative real-time polymerase chain reaction (qRT-PCR) are shown in our previous research ( Chen et al, 2020 ). cDNA was amplified with an Applied Biosystems QuantStudio 5 Real-Time PCR instrument.…”

Section: Methodsmentioning

confidence: 99%

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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Background: RNA methylation modification plays an important role in immune regulation. m7G RNA methylation is an emerging research hotspot in the RNA methylation field. However, its role in the tumor immune microenvironment of kidney renal clear cell carcinoma (KIRC) is still unclear.Methods: We analyzed the expression profiles of 29 m7G regulators in KIRC, integrated multiple datasets to identify a novel m7G regulator-mediated molecular subtype, and developed the m7G score. We evaluated the immune tumor microenvironments in m7G clusters and analyzed the correlation of the m7G score with immune cells and drug sensitivity. We tested the predictive power of the m7G score for prognosis of patients with KIRC and verified the predictive accuracy of the m7G score by using the GSE40912 and E-MTAB-1980 datasets. The genes used to develop the m7G score were verified by qRT-PCR. Finally, we experimentally analyzed the effects of WDR4 knockdown on KIRC proliferation, migration, invasion, and drug sensitivity.Results: We identified three m7G clusters. The expression of m7G regulators was higher in cluster C than in other clusters. m7G cluster C was related to immune activation, low tumor purity, good prognosis, and low m7G score. Cluster B was related to drug metabolism, high tumor purity, poor survival, and high m7G score. Cluster A was related to purine metabolism. The m7G score can well-predict the prognosis of patients with KIRC, and its prediction accuracy based on the m7G score nomogram was very high. Patients with high m7G scores were more sensitive to rapamycin, gefitinib, sunitinib, and vinblastine than other patients. Knocking down WDR4 can inhibit the proliferation, migration, and invasion of 786-0 and Caki-1 cells and increase sensitivity to sorafenib and sunitinib.Conclusion: We proposed a novel molecular subtype related to m7G modification and revealed the immune cell infiltration characteristics of different subtypes. The developed m7G score can well-predict the prognosis of patients with KIRC, and our research provides a basis for personalized treatment of patients with KIRC.

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Section: Methodsmentioning

confidence: 99%

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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“…In particular, point mutation p.H101Q seems to be fundamental for membrane insertion of CLIC2 protein, suggesting that p.H101Q may be a disease-causing mutation, the first correlated with CLIC superfamily [ 9 ]. As for CLIC1 and CLIC2 proteins, also CLIC3 was found to be overexpressed in bladder cancer [ 10 ], pancreatic cancer [ 11 ], and metastatic breast cancer [ 12 ]. Its role in carcinogenesis was demonstrated to be correlated with the activity of CLIC1 as glutathione-dependent oxidoreductase activity that drive angiogenesis and increases invasiveness of cancer cells with transglutaminase-2 in ovarian cancer [ 13 ].…”

Section: Clic Proteins a Focus On Clic1mentioning

confidence: 99%

Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) as a Potential Biomarker for Personalized Medicine

Cianci

Verduci

2021

JPM

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Identification of potential pathological biomarkers has proved to be essential for understanding complex and fatal diseases, such as cancer and neurodegenerative diseases. Ion channels are involved in the maintenance of cellular homeostasis. Moreover, loss of function and aberrant expression of ion channels and transporters have been linked to various cancers, and to neurodegeneration. The Chloride Intracellular Channel 1 (CLIC1), CLIC1 is a metamorphic protein belonging to a partially unexplored protein superfamily, the CLICs. In homeostatic conditions, CLIC1 protein is expressed in cells as a cytosolic monomer. In pathological states, CLIC1 is specifically expressed as transmembrane chloride channel. In the following review, we trace the involvement of CLIC1 protein functions in physiological and in pathological conditions and assess its functionally active isoform as a potential target for future therapeutic strategies.

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“…Our findings imply that more research into the involvement of CLIC3 in cellular senescence is warranted. Although there is currently a bioinformation-based study on the role of CLIC3 in bladder cancer, the study only conducted a simple expression difference analysis and clinical correlation of CLIC3 [ 15 ]. In the validation part of our study, we further explored the protein expression of CLIC3 and the change of Wnt pathway in BC cell lines after CLIC3 silencing.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed experimental details were carried out according to the methods in previous reference [ 14 ]. The sequences of the primers used for qRT-PCR are as follows: CLIC3 (forward: 5′-CAGATCGAGGACTTTCTGGAG-3′, reverse: 5′-GGAGAACTTGTGGAAAACGTC-3′) and GAPDH (forward: 5′-CAGGAGGCATTGCTGATGAT-3′, reverse: 5′-GAAGGCTGGGGCTCATTT-3′) [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Derivation and Comprehensive Analysis of Aging Patterns in Patients with Bladder Cancer

et al. 2021

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Background. Aging is an essential risk factor for cancer. However, aging-related genes (ARGs) have not been comprehensively analyzed in bladder cancer (BC). Therefore, the study is aimed at derivating a risk stratification system for BC patients based on ARGs. Methods. Public databases were used to acquire ARGs sets, transcriptome files, and clinical data. The “limma” package was then used to screen for differential ARGs while also using univariate Cox regression analysis to explore for prognostic ARGs. The “ConsensusClusterPlus” package was used to perform aging patterns in BC patients based on the above prognostic ARGs. Subsequently, aging patterns were investigated in survival prediction, mutation landscape, immunotherapy, immunological checkpoints, and immune microenvironment. We likewise utilized gene enrichment analysis to explore the biological functions that were behind the findings. To construct a risk signature and nonogram for prognostic prediction, we used LASSO and Cox regression analysis based on differential genes in aging patterns. In addition, we plotted a nomogram and validate the accuracy of the risk signature in GEO and TCGA cohorts. We explored the possible biological mechanism using GSEA analysis and preliminarily identified a hub gene using PPI network. Finally, we validated the expression of hub gene in BC cell lines. Results. We screened 84 downregulated ARGs, 74 upregulated ARGs, and 32 prognostic ARGs in the human aging genome resource. The aging patterns based on prognostic genes had excellent survival prediction ( p < 0.001 ) and discriminatory ability in 405 BC patients. In addition, we found no significant differences in aging patterns in mutation analysis, which were all characterized by TP53, TTN, and KMT2D mutations. It is worth noting that cluster B in the aging patterns has a better response to immunotherapy and a more active immune microenvironment ( p < 0.05 ). In addition, gene enrichment analysis showed that aging patterns may be related to biological processes such as Staphylococcus aureus infection, phagosome, and cytokine-cytokine receptor interaction. Subsequently, we constructed a risk signature based on 16 differential genes from different aging patterns and had good survival prediction ability in both GEO and TCGA cohort. Specifically, survival analysis revealed a significantly shorter survival time in the high-risk group than in the low-risk group (TCGA and GEO, p < 0.001 ). In addition, AUC values in the ROC analysis predicted 1, 3, and 5 years in TCGA cohort that are 0.713, 0.714, and 0.738, respectively. AUC values predicted 1, 3, and 5 years in GEO cohort that are 0.606, 0.663, and 0.718, respectively. There is no doubt that risk score was an independent prognostic factor from results of multivariate Cox regression analysis in BC patients ( p < 0.001 ). There were also significant differences in immune cell infiltration, immune checkpoint, and immune score between the two groups ( p < 0.05 ), but it should not be ignored that the correlation with the HLA expression was weak. Finally, we identified and validated CLIC3 as a hub gene that may be involved in the Wnt signaling pathway, etc. Conclusion. We provided robust evidences that aging patterns based on ARGs can guide targeted therapy and survival prediction in BC patients.

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Prognostic value of CLIC3 mRNA overexpression in bladder cancer

Cited by 11 publications

References 25 publications

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) as a Potential Biomarker for Personalized Medicine

Derivation and Comprehensive Analysis of Aging Patterns in Patients with Bladder Cancer

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