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

Meng, Zhishang; Chen, Yanzhu; Wu, Wenyi; Yan, Bin; Zhang, Lusi; Chen, Huihui; Meng, Yongan; Liang, Youling; Yao, Xiaofeng; Luo, Jing

doi:10.3389/fimmu.2022.754645

Cited by 13 publications

(8 citation statements)

References 58 publications

(74 reference statements)

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“…At present, studies of UVM have elucidated many mechanisms and found new predictors and potential targets (62)(63)(64), but no specific mechanism of the B7 family has been studied. To explore the mechanism of B7 family, we performed GO and KEGG analysis.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Chen

Zheng²,

Zhang³

et al. 2022

Front. Immunol.

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BackgroundUveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear.MethodsData were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat.ResultsThe expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells.ConclusionsDysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Chen

Zheng²,

Zhang³

et al. 2022

Front. Immunol.

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“…Peculiarly, micrometastatic lesions were devoid of CSCs, but on the other hand, de novo CSCs were indeed present in overt metastases [ 55 ]. After extravasation, metastatic colonization is further stimulated by MET, which triggers the re-expression of E-cadherin and the downregulation of Prrx1, which subsequently decreases Snail 1 expression and leads to the re-acquisition of an epithelial phenotype and epithelial morphology [ 56 , 57 ].…”

Section: Role Of Circulating Tumors Cells With Cancer Stem Cell Prope...mentioning

confidence: 99%

Role of Epithelial-to-Mesenchymal Transition for the Generation of Circulating Tumors Cells and Cancer Cell Dissemination

Nzeteu

Geismann

Arlt

et al. 2022

Cancers

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Tumor-related death is primarily caused by metastasis; consequently, understanding, preventing, and treating metastasis is essential to improving clinical outcomes. Metastasis is mainly governed by the dissemination of tumor cells in the systemic circulation: so-called circulating tumor cells (CTCs). CTCs typically arise from epithelial tumor cells that undergo epithelial-to-mesenchymal transition (EMT), resulting in the loss of cell–cell adhesions and polarity, and the reorganization of the cytoskeleton. Various oncogenic factors can induce EMT, among them the transforming growth factor (TGF)-β, as well as Wnt and Notch signaling pathways. This entails the activation of numerous transcription factors, including ZEB, TWIST, and Snail proteins, acting as transcriptional repressors of epithelial markers, such as E-cadherin and inducers of mesenchymal markers such as vimentin. These genetic and phenotypic changes ultimately facilitate cancer cell migration. However, to successfully form distant metastases, CTCs must primarily withstand the hostile environment of circulation. This includes adaption to shear stress, avoiding being trapped by coagulation and surviving attacks of the immune system. Several applications of CTCs, from cancer diagnosis and screening to monitoring and even guided therapy, seek their way into clinical practice. This review describes the process leading to tumor metastasis, from the generation of CTCs in primary tumors to their dissemination into distant organs, as well as the importance of subtyping CTCs to improve personalized and targeted cancer therapy.

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“…Paired related homeobox 1 (PRRX1), is a key member of the homomeric protein pairing family located at the nucleus. PRRX1 mediates cancer cell invasion and metastasis by starting EMT ( Meng et al, 2022 ). In addition, PRRX1 impacts the division and metastasis of various tumor cells via Wnt/β-catenin and Notch pathways, and maintains the characteristics of tumor stem cells to promote EMT ( Du et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma

et al. 2023

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Background: Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM.Methods: Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms.Results: Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays.Conclusion: The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.

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

Cited by 13 publications

References 58 publications

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Role of Epithelial-to-Mesenchymal Transition for the Generation of Circulating Tumors Cells and Cancer Cell Dissemination

Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma

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