Identification of a Recurrence Signature and Validation of Cell Infiltration Level of Thyroid Cancer Microenvironment

Zhang, Liang; Wang, Ying; Li, Xiaobo; Yang, Wang; Wu, Kaile; Wu, Jing; Liu, Yehai

doi:10.3389/fendo.2020.00467

Cited by 13 publications

(14 citation statements)

References 48 publications

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“…Consistent with the results of a previous study [ 14 ], the expression level of FXYD6 was positively correlated with chemotherapy sensitivity in the present study. Additionally, FXYD6 was reported to form a panel in combination with another six genes to predict early relapse in thyroid cancer [ 43 ]. These findings indicate that FXYD6 might prove to be a promising indicator of the risk of recurrence in CRC.…”

Section: Discussionmentioning

confidence: 99%

FXYD6 Regulates Chemosensitivity by Mediating the Expression of Na+/K+-ATPase α1 and Affecting Cell Autophagy and Apoptosis in Colorectal Cancer

Luo

Liu

Chen

et al. 2021

BioMed Research International

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Purpose. Chemoresistance is a challenge of improving chemotherapeutic efficacy and prolonging survival time for patients with colorectal cancer (CRC); it is the major cause of frequent recurrence, rapid metastasis, and poor prognosis for CRC patients. FXYD6 is a regulator of Na+/K+-ATPase which is depressed in chemoresistant CRC patients. However, the biological roles of FXYD6 on regulating chemoresistance in CRC are still unclear. Methods. GSE3964 and GSE69657 from GEO DataSets were used to analyze the relationship of genes and chemoresistance. The FXYD6 expression level was detected by western blotting and real-time PCR and also analyzed from TCGA DataSet. To investigate the functional role of FXYD6 and ATP-α1, FXYD6 and ATP-α1 functional cell models were constructed. Drug sensitivity and cell proliferation were performed by MTT assay. Autophagy and apoptosis were conducted by autophagy fluorescence analysis and flow cytometric analysis, respectively. Autophagy and apoptosis markers were tested by western blotting. Results. FXYD6 was downregulated in CRC resistant patients and irinotecan- (Iri-) resistant SW620 cells (SW620/Iri). FXYD6 silence inhibited cell apoptosis and enhanced prosurvival autophagy, whereas FXYD6 overexpression produced the opposite effect which alleviated the drug resistance to irinotecan and oxaliplatin of CRC cells. FXYD6 regulates chemosensitivity by mediating the expression of Na+/K+-ATPase α1 and affecting cell autophagy and apoptosis in colorectal cancer. Conclusion. FXYD6 functions as a chemosensitivity regulator which may predict the curative effect of chemotherapy in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

FXYD6 Regulates Chemosensitivity by Mediating the Expression of Na+/K+-ATPase α1 and Affecting Cell Autophagy and Apoptosis in Colorectal Cancer

Luo

Liu

Chen

et al. 2021

BioMed Research International

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“…However, few studies on GGCT have been reported in thyroid cancer research. Intriguingly, a previous study based on bioinformatics showed a 7-gene panel including GGCT exhibited significantly superior accuracy in predicting relapse-free survival and the status of immunocyte infiltration in PTC ( 32 ). Nevertheless, it remained unknown if GGCT upregulation is simply a concomitant product of tumor progression or is selectively upregulated during cancer initiation and development, and thereby serves as an oncogenic accelerator.…”

Section: Discussionmentioning

confidence: 92%

MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44

Zhang

et al. 2022

Endocrinology

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Papillary thyroid cancer (PTC) is the most common endocrine malignancy, despite marked achieves in recent decades, the mechanisms underlying the pathogenesis and progression for PTC are incomplete. Accumulating evidence show that γ-glutamylcyclotransferase (GGCT), an enzyme participated in glutathione homeostasis that is elevated in multiple types of tumors, represents an attractive therapeutic target. Using bioinformatics, immunohistochemistry, qRT-PCR and western blot assays, we found that GGCT expression was upregulated in PTC, correlated with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the growth and metastasis ability of PTC cells both in vitro and in vivo and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP2 and MMP9) while increased epithelial marker (E-cadherin) in PTC cells. We confirmed binding of miR-205-5p on the 3’-UTR regions of GGCT by dual luciferase reporter assay, RNA-RNA pull down assay. Delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found GGCT interacted with and stabilized CD44 in PTC cells by co-immunoprecipitation and immunohistochemistry assays. Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.

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“…After that, a nomogram was constructed to screen out the relatively high-risk patients in clinical practice; and this population might need extended resection and lymphadenectomy. Nomograms are widely used to predict prognosis, skip metastasis, and central lymph node metastasis in thyroid carcinoma [ 59 – 61 ]. To give clinicians a practical tool for individualized prognosis prediction, we constructed a nomogram based on the independent factors in the multivariate Cox regression analysis.…”

Section: Discussionmentioning

confidence: 99%

A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma

Yuan

et al. 2022

World J Surg Onc

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Background Numerous studies have implicated autophagy in the pathogenesis of thyroid carcinoma. This investigation aimed to establish an autophagy-related gene model and nomogram that can help predict the overall survival (OS) of patients with differentiated thyroid carcinoma (DTHCA). Methods Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. We also downloaded autophagy-related genes (ARGs) from the Gene Set Enrichment Analysis website and the Human Autophagy Database. First, we assigned patients into training and testing groups. R software was applied to identify differentially expressed ARGs for further construction of a protein-protein interaction (PPI) network for gene functional analyses. A risk score-based prognostic risk model was subsequently developed using univariate Cox regression and LASSO-penalized Cox regression analyses. The model’s performance was verified using Kaplan-Meier (KM) survival analysis and ROC curve. Finally, a nomogram was constructed for clinical application in evaluating the patients with DTHCA. Finally, a 7-gene prognostic risk model was developed based on gene set enrichment analysis. Results Overall, we identified 54 differentially expressed ARGs in patients with DTHCA. A new gene risk model based on 7-ARGs (CDKN2A, FGF7, CTSB, HAP1, DAPK2, DNAJB1, and ITPR1) was developed in the training group and validated in the testing group. The predictive accuracy of the model was reflected by the area under the ROC curve (AUC) values. Univariate and multivariate Cox regression analysis indicated that the model could independently predict the prognosis of patients with THCA. The constrained nomogram derived from the risk score and age also showed high prediction accuracy. Conclusions Here, we developed a 7-ARG prognostic risk model and nomogram for differentiated thyroid carcinoma patients that can guide clinical decisions and individualized therapy.

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Identification of a Recurrence Signature and Validation of Cell Infiltration Level of Thyroid Cancer Microenvironment

Cited by 13 publications

References 48 publications

FXYD6 Regulates Chemosensitivity by Mediating the Expression of Na+/K+-ATPase α1 and Affecting Cell Autophagy and Apoptosis in Colorectal Cancer

FXYD6 Regulates Chemosensitivity by Mediating the Expression of Na+/K+-ATPase α1 and Affecting Cell Autophagy and Apoptosis in Colorectal Cancer

MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44

A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma

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