Prognostic Significance of β-Catenin Expression in Osteosarcoma: A Meta-Analysis

Xie, Xiaoxiao; Li, Yumei; Zhu, Haixia; Kuang, Zhixing; Chen, Deta; Fan, Tao

doi:10.3389/fonc.2020.00402

Cited by 10 publications

(4 citation statements)

References 35 publications

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“…Here, we found an inverse correlation of WNT/β-catenin pathway enrichment with immune infiltration (ICR score) in OS with a prognostic value in the same cohort, in which the high enrichment of WNT/β-catenin pathway was associated with worse prognosis. In addition to the association with low immune infiltration and overall survival; a meta-analysis performed by Xie et al suggested that overexpression of β-catenin is an indicator of metastasis for osteosarcoma patients [ 60 ]. Several clinical trials are ongoing applying the combination of immunotherapy with WNT/β-catenin signaling inhibitors for the treatment of various tumors (Y. Zhang and Wang 2020).…”

Section: Discussionmentioning

confidence: 99%

The immune landscape of solid pediatric tumors

Sherif

Roelands

Mifsud

et al. 2022

J Exp Clin Cancer Res

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Background Large immunogenomic analyses have demonstrated the prognostic role of the functional orientation of the tumor microenvironment in adult solid tumors, this variable has been poorly explored in the pediatric counterpart. Methods We performed a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types (408 patients): Wilms tumor (WLM), neuroblastoma (NBL), osteosarcoma (OS), clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RT). We assessed the performance of the Immunologic Constant of Rejection (ICR), which captures an active Th1/cytotoxic response. We also performed gene set enrichment analysis (ssGSEA) and clustered more than 100 well characterized immune traits to define immune subtypes and compared their outcome. Results A higher ICR score was associated with better survival in OS and high risk NBL without MYCN amplification but with poorer survival in WLM. Clustering of immune traits revealed the same five principal modules previously described in adult tumors (TCGA). These modules divided pediatric patients into six immune subtypes (S1-S6) with distinct survival outcomes. The S2 cluster showed the best overall survival, characterized by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration, while the reverse was observed in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS. Conclusions We demonstrated that extracranial pediatric tumors could be classified according to their immune disposition, unveiling similarities with adults’ tumors. Immunological parameters might be explored to refine diagnostic and prognostic biomarkers and to identify potential immune-responsive tumors.

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Section: Discussionmentioning

confidence: 99%

The immune landscape of solid pediatric tumors

Sherif

Roelands

Mifsud

et al. 2022

J Exp Clin Cancer Res

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“…Increasingly data suggest the abnormal activation of the hedgehog (Hh) pathway that has a pivotal role in signaling during embryogenesis, in OS [ 33 , 34 ] and several therapeutic strategies have been developed to target this pathway [ 35 , 36 ]. The prognostic and predictive impact of the expression of p16 [ 37 ], HER2 [ 38 ] and β-catenin [ 39 ] have also been investigated with some promising results.…”

Section: Osteosarcoma and Macrophage Functionmentioning

confidence: 99%

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Cersosimo

Lonardi

Bernardini

et al. 2020

IJMS

140

116

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Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.

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“…Differential expression analysis showed 12 downregulated genes (mostly associated with the negative regulation of transcription: NFKBIB, BTRC, CREBBP, HDAC1, NCOR2, and FBXW11) and 19 upregulated genes [mostly associated with protein ubiquitination (SOCS1, RBX1, RPS27A, UBB, UBA52, and UBE2N), positive regulation of cell proliferation (CTNNB1, NRAS, HRAS, CDKN1A, and STAT3), and cell surface receptor signaling pathways (IL6, IFNA5, IFNA7, IFNA16, and NGF) in OS samples compared to controls. Several of these genes have already been associated with OS pathophysiology [149,[163][164][165][166][167][168][169][170][171][172][173][174][175][176][177]. Moreover, KEGG functional enrichment was assessed through STRING v12 (available at https://string-db.org/ accessed on 17 April 2024) and showed that under-expressed genes belonged mainly to MAPK and WNT signaling pathways, while upregulated genes belonged to the PI3K/AKT and JAK/STAT cascades (Figure 6C), reinforcing the concept of NF-κB as a common player underneath OS establishment and progression.…”

Section: Osteosarcomamentioning

confidence: 99%

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Medeiros,

Guenka,

Bastos

et al. 2024

Pharmaceuticals

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Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

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Prognostic Significance of β-Catenin Expression in Osteosarcoma: A Meta-Analysis

Cited by 10 publications

References 35 publications

The immune landscape of solid pediatric tumors

The immune landscape of solid pediatric tumors

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

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