MFNG is an independent prognostic marker for osteosarcoma

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Abstract

Background

Osteosarcoma (OS) has been the most common malignancy of the bone in children and adolescents, and the unsatisfactory prognosis of OS sufferers has long been a hard nut. Here, we delved into the markers with a prognostic value for predicting the prognosis of OS patients.

Methods

The messenger RNA (mRNA) sequencing data and clinical data of OS were retrieved from a Gene Expression Omnibus (GEO) dataset (GSE39058). Next, prognosis-related genes (PRGs) were filtered with the aid of Kaplan–Meier (K-M) curves and Cox regression analysis (CRA). Later, Gene Ontology (GO) biological process analysis was used in verifying the function of different genes. CCK-8 and cell apoptosis assay were performed to evaluate the function of MFNG in U2OS cells.

Results

Among the obtained genes, Manic Fringe ( MFNG) had the closest relevance to prognosis and clinical traits, thus becoming the research object herein. In light of the expression level of MFNG, patients fell into high- and low- MFNG groups. Patients with elevated MFNG expression had a worse prognosis, according to the survival analysis. It was unveiled by the univariate and multivariate analyses that MFNG expression was an independent adverse prognostic factor for disease-free survival in OS patients (p = 0.006). Meanwhile, MFNG expression was linked to gender and tumor recurrence, and it was higher in patients with OS recurrence. Moreover, overexpression of MFNG promoted the cell proliferation and inhibited the cell apoptosis of U2OS cells.

Conclusions

The expression level of MFNG negatively correlated with OS progression, and as an independent adverse prognostic factor for disease-free survival in OS patients. Moreover, MFNG regulated the cell proliferation and apoptosis of OS cells.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40001-023-01139-x.

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Most cited references 41

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The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.

Jeffrey A. Engelman, Ji Wei Luo, Lewis Cantley (2006)

Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.

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Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort

Sigbjørn Smeland, Stefan S. Bielack, Jeremy Simon Whelan … (2019)

Background High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. Methods Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. Results For all registered patients at a median follow-up of 54 months (interquartile range: 38–73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57–61%) and 54% (95% CI: 52–56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95–2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38–2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10–2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33–0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52–0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77–81%) and 71% (95% CI: 68–73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76–2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. Conclusions In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.

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Osteosarcoma, Chondrosarcoma, and Chordoma

Jeremy S. Whelan, Lara Davis (2018)

Osteosarcoma (OS), chondrosarcoma, and chordoma are characterized by multiple challenges to the investigator, clinician, and patient. One consequence of their rarity among sarcomas, as well as their biologic and clinical heterogeneity, is that management guidelines are inadequate to inform the range of individual patient-treatment decisions from diagnosis, approaches to surgery, chemotherapy, radiotherapy, treatment of recurrence, palliative care, and quality of survivorship. Of high-grade sarcomas, OSs are among the most curable, with more than two-thirds of patients with localized disease likely to achieve long-term survival. Neoadjuvant chemotherapy comprising cisplatin, doxorubicin, and methotrexate with intercalated surgery is the standard of care for resectable OS in those younger than 40 years. Outcomes for OS presenting with unresectable metastases or recurrent disease, or in those older than 40 years are generally poor. Overall results have improved little for all patients with OS, and new treatments are needed. Surgical resection remains the cornerstone of management for chondrosarcoma and chordoma. However, the application of new biologic insights to therapeutic development indicates that improved treatments may soon be routine for patients with chondrosarcoma and chordoma for whom surgery alone is inadequate. For all these uncommon diseases, patients should be offered specialist expert care delivered by experienced multidisciplinary teams in high-volume centers.

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Author and article information

Contributors

Qi Zhou: changzhouzhouqi@163.com

Journal

Journal ID (nlm-ta): Eur J Med Res

Journal ID (iso-abbrev): Eur J Med Res

Title: European Journal of Medical Research

Publisher: BioMed Central (London )

ISSN (Print): 0949-2321

ISSN (Electronic): 2047-783X

Publication date (Electronic): 26 July 2023

Publication date PMC-release: 26 July 2023

Publication date Collection: 2023

Volume: 28

Electronic Location Identifier: 256

Affiliations

GRID grid.410745.3, ISNI 0000 0004 1765 1045, Department of Orthopaedics, , Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, ; 25 Heping Bei Lu, Tianning District, Changzhou, 213000 Jiangsu China

Article

Publisher ID: 1139

DOI: 10.1186/s40001-023-01139-x

PMC ID: 10369729

PubMed ID: 37496053

SO-VID: 8718ee50-407c-4846-a2e3-e5a98629a15f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 7 July 2022

Date accepted : 13 May 2023

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ScienceOpen disciplines: Medicine

Keywords: mfng,osteosarcoma,prognosis,recurrence,fringe

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ScienceOpen disciplines: Medicine

Keywords: mfng, osteosarcoma, prognosis, recurrence, fringe

MFNG is an independent prognostic marker for osteosarcoma

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Most cited references 41

The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort

Osteosarcoma, Chondrosarcoma, and Chordoma

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