&lt;p&gt;The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma&lt;/p&gt;

Tian, Xiaodong; He, Yinfeng; Han, Zhe; Su, Hongmin; Chu, Chao

doi:10.2147/cmar.s229441

Cited by 11 publications

(9 citation statements)

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“…Osteosarcoma patients are typically treated with chemotherapy, radiotherapy, and surgery. Although recent clinical studies have shown that adjuvant chemotherapy can improve the survival rate of such patients, the prognosis remains poor (Tian et al, 2019;Wang J. et al, 2019). Therefore, the development of improved management and risk stratification methods, as well as the identification of robust prognostic biomarkers, are of high clinical importance.…”

Section: Introductionmentioning

confidence: 99%

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Zhang

et al. 2021

Front. Mol. Biosci.

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BackgroundOsteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients.MethodsWe obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration.ResultsWe initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells.ConclusionThe autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.

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Section: Introductionmentioning

confidence: 99%

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Zhang

et al. 2021

Front. Mol. Biosci.

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“…In addition, the same researchers found upregulated expression of claudin-12 in lung squamous cell carcinoma (SqCC) tissues, suggesting the CLDN12 gene as a proto-oncogene in SqCC [ 17 ]. Similarly, Tian et al concluded that cytoplasmic overexpression of claudin-12 promotes the proliferation and migration ability of osteosarcoma cells [ 14 ]. Taking into account the tissue-specific expression of the claudin proteins, Jiang et al [ 21 ] noted that they could be used as prognostic and diagnostic biomarkers, e.g., claudin-1 for colon cancers, claudin-3 for ovarian cancers, claudin-10 for hepatocellular carcinomas, etc.…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulated expression of claudins has been reported in various cancers, suggesting that they may have an important role in the migration, invasion, and metastasis of cancer cells [ 3 , 13 , 14 , 15 , 16 , 17 ]. More than 90% of cancer-related deaths are due to metastases [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that in vitro expression of claudin-12 is up-regulated by vitamin D, suggesting an essential role for this claudin in Ca 2+ absorption between intestinal epithelial cells [12]. Dysregulated expression of claudins has been reported in various cancers, suggesting that they may have an important role in the migration, invasion, and metastasis of cancer 2 of 13 cells [3,[13][14][15][16][17]. More than 90% of cancer-related deaths are due to metastases [18].…”

Section: Introductionmentioning

confidence: 99%

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Tight Junction Protein Claudin-12 Is Involved in Cell Migration during Metastasis

et al. 2021

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Claudins are important components of the tight junctions determining barrier properties, cell polarity, and paracellular permeability. Although many functions of claudins in cancer cells have not been elucidated, recent studies have shown that claudins play an important role in cell migration and metastasis. Loss of epithelial/endothelial integrity, disruption of tight junctions, and increased paracellular leakage are often observed during metastasis. The aim of our study was to investigate the involvement of claudin-12 in the process of cell migration as well as to evaluate the possibility of using this protein as a specific target for the regulation of tumorigenesis. We have performed immunocytochemistry assays to detect the expression of claudin-12 in different epithelial/endothelial human cell lines, and selected three (A549, LS180, and HeLa) for further experiments. Using transwell chamber migration assays, we found that anti-claudin-12 antibodies inhibited both the migration and proliferation of claudin-12 expressing cells (A549 and LS180), inducing apoptosis, as well as the migration capacity of Jurkat cells through the monolayers formed from A549 or LS180 cells. In addition, co-cultures of Jurkat cells on monolayers from A549 or LS180 cells, in the presence of synthetic claudin-12 peptides representing the extracellular domains of the claudin-12 protein, also reduced the number of migrated Jurkat cells. Two of the tested peptides (p5 and p6) almost completely blocked the migration of Jurkat cells. All migrated Jurkat cells expressed LFA-1 and CD62L, but not CD44. Thus, claudin-12 is a suitable biomarker for tumor progression and metastasis and an attractive target for antitumor therapy. Anti-claudin-12 antibodies and competitive inhibitory peptides could be useful in the therapeutic approach applied to cancer metastasis in tissues expressing claudin-12.

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“…Abnormality in cytokine-cytokine receptor interaction is related to OS genesis and poor prognosis (46,47). Abnormality in tight junction promotes a malignant phenotype of OS cells and causes poor prognosis (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Identification of a 7-mRNA signature as a prognostic biomarker in pediatric osteosarcoma

Cui¹,

Guo²,

Jin³

2020

Transl Cancer Res TCR

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Background:The aim of the present study was to establish a prognostic model for the survival of children with osteosarcoma (OS). Methods:The mRNA expression and clinical characteristics of pediatric patients with OS were extracted from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. After genes with differential mRNA expression were identified, univariate and multivariate Cox analyses were performed, and a prognostic model of pediatric OS was established. The prognostic values of a 7-mRNA signature were evaluated using the receiver-operating characteristic (ROC) curve in pediatric patients with OS.Results: A total of 19,496 differentially expressed mRNAs were identified, including 267 upregulated mRNAs and 104 downregulated mRNAs. After univariate and multivariate Cox analyses, seven mRNA species (SCGB3A1, MUC17, ADH1B, KRT83, RP1-37E16.12, FIGF, and SFTPD) were found to be closely associated with survival. These mRNA species were mainly enriched in glycolysis/gluconeogenesis, arachidonic acid metabolism, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, tight junction, and complement and coagulation cascade pathways. A predictive model using the sum of independent prognostic values of the seven mRNA species as the risk score was proposed. The risk score was calculated as follows: risk score = 0.242257 × SCGB3A1 + 0.168999 × MUC17 + 0.415514 × ADH1B + 0.488864 × KRT83 + 0.360864 × RP1-37E16.12 -0.2991 × FIGF -0.39576 × SFTPD. Pediatric patients with OS were assigned to low-and high-risk groups based on the risk score. The ROC curve analysis showed that the 7-mRNA prediction model performed well [area under the curve (AUC): 0.858].Conclusions: A 7-mRNA signature has the potential to predict the prognosis of pediatric patients with OS, and therefore warrants further validation.

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<p>The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma</p>

Cited by 11 publications

References 51 publications

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Tight Junction Protein Claudin-12 Is Involved in Cell Migration during Metastasis

Identification of a 7-mRNA signature as a prognostic biomarker in pediatric osteosarcoma

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