PRRX1 promotes malignant properties in human osteosarcoma

Joko, Ryoji; Yamada, Daisuke; Nakamura, Masahiro; Yoshida, Aki; Takihira, Shota; Takao, Tomoka; Ming, Liao; Sato, Kohei; Itö, Tatsuo; Kunisada, Toshiyuki; Nakata, Eiji; Takarada, Takeshi

doi:10.1016/j.tranon.2020.100960

Cited by 8 publications

(12 citation statements)

References 46 publications

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“…Osteosarcoma is an aggressive tumor of bone and prone to DM, occurring in 15-40% of patients (22,23). Almost all deaths in patients with osteosarcoma are caused by DM (24,25).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

et al. 2021

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BackgroundOsteosarcoma is the most common bone cancer, mainly occurring in children and adolescents, among which distant metastasis (DM) still leads to a poor prognosis. Although nomogram has recently been used in tumor areas, there are no studies focused on diagnostic and prognostic evaluation of DM in primary osteosarcoma patients.MethodsThe data of osteosarcoma patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in osteosarcoma patients, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors of osteosarcoma patients with DM. We then established two novel nomograms and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultA total of 1,657 patients with osteosarcoma were included, and 267 patients (16.11%) had DM at the time of diagnosis. The independent risk factors for DM in patients with osteosarcoma include age, grade, T stage, and N stage. The independent prognostic factors for osteosarcoma patients with DM are age, chemotherapy and surgery. The results of ROC curves, calibration, DCA, and Kaplan–Meier (K-M) survival curves in the training, validation, and expanded testing sets, confirmed that two nomograms can precisely predict occurrence and prognosis of DM in osteosarcoma patients.ConclusionTwo nomograms are expected to be effective tools for predicting the risk of DM for osteosarcoma patients and personalized prognosis prediction for patients with DM, which may benefit clinical decision-making.

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“…Osteosarcoma is an aggressive tumor of bone and prone to DM, occurring in 15-40% of patients (22,23). Almost all deaths in patients with osteosarcoma are caused by DM (24,25).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

et al. 2021

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“…Instead, we defined a large number of Tnmd+ tenocytes (Figure 3C), Cd248+ pericytes and a small cluster of muscle stem cells that uniquely expressed Pax7. In the hind limbs, we also found many Mylpf+ muscle cells and Prrx1+ limb bud mesenchymal cells 45 . We observed multiple cell-type remodeling events in the heart.…”

Section: Identification Of Neotenic and Metamorphosed Axolotl Cell Transcriptome Subtypesmentioning

confidence: 65%

The single-cell transcriptional landscape of the axolotl

Zhang

Weigao

et al. 2021

Preprint

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The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis.

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“…Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of UM cells in vitro. PRRX1 protein is a member of the family of paired-type homeobox transcription factors, which have important functions in the regulation of developmental morphogenetic processes, such as vasculogenesis and organogenesis (37). PRRX1 is expressed in all known fibroblast subtypes.…”

Section: Discussionmentioning

confidence: 99%

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

Meng

Chen

et al. 2022

Front. Immunol.

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, PRRX1 as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO–Cox regression model. A prognostic model based on PRRX1 was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High PRRX1 expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that PRRX1 was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of PRRX1 was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high PRRX1 expression correlated with angiogenesis, epithelial–mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B in vitro. Taken together, these findings indicated that increased PRRX1 expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that PRRX1 promotes malignant progression of UM by facilitating EMT, suggesting that PRRX1 may be a potential target for UM therapy.

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PRRX1 promotes malignant properties in human osteosarcoma

Cited by 8 publications

References 46 publications

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

The single-cell transcriptional landscape of the axolotl

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

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