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人类与犬骨肉瘤中差异表达基因的比较

Comparison of Differentially Expressed Genes in Human and Canine Osteosarcoma.

作者信息

Jackson-Oxley Jorja, Alibhai Aziza A, Guerin Jack, Thompson Rachel, Patke Rodhan, Harris Anna E, Woodcock Corinne L, Varun Dhruvika, Haque Maria, Modikoane Tinyiko K, Kumari Amber A, Lothion-Roy Jennifer, Brot Simone de, Dunning Mark D, Jeyapalan Jennie N, Mongan Nigel P, Rutland Catrin S

机构信息

School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham LE12 5RD, UK.

Biodiscovery Institute, Faculty of Medicine and Health Science, University of Nottingham, Nottingham NG7 2RD, UK.

出版信息

Life (Basel). 2025 Jun 12;15(6):951. doi: 10.3390/life15060951.

DOI:10.3390/life15060951
PMID:40566602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12194233/
Abstract

Osteosarcoma (OSA) is the most prevalent bone malignancy in people and dogs. Current survival rates show the need for advances in novel therapies to help overcome the growth, survival and metastatic progression of the cancer. Canine models are often used to advance prognostic and treatment opportunities for OSA due to the similarities in the disease between species. This study focusses on the genetic and molecular similarities of OSA between human and canine specimens. Differentially expressed genes (DEGs) were compared and identified in canine and human OSA tumours, revealing 86 common genes, 36 having high and 50 having low expression. Further immunohistochemical analysis of the corresponding proteins of three identified DEGs (ASPN, STK3, BAMBI) allowed for the visualisation of protein expression in canine OSA tissues (n = 19). Overall nuclear and cytoplasmic H-scores were generated, and nuclear and cytoplasmic scores in males and females and in different anatomical locations (axial versus appendicular) were also investigated, presenting unique opportunities to understand the expression in this cancer type. This study contributes to a deeper knowledge of genetic pathways changes and identifies avenues for the diagnosis, prognosis and treatment of OSA in people and dogs, whilst encompassing the One Health concept in medicine.

摘要

骨肉瘤(OSA)是人和犬类中最常见的骨恶性肿瘤。目前的生存率表明需要在新型疗法方面取得进展,以帮助克服癌症的生长、存活和转移进展。由于物种间疾病的相似性,犬类模型常被用于推进骨肉瘤的预后和治疗机会。本研究聚焦于人类和犬类标本中骨肉瘤的遗传和分子相似性。对犬类和人类骨肉瘤肿瘤中的差异表达基因(DEGs)进行了比较和鉴定,发现了86个共同基因,其中36个高表达,50个低表达。对三个鉴定出的DEGs(ASPN、STK3、BAMBI)的相应蛋白质进行进一步免疫组织化学分析,可观察犬类骨肉瘤组织(n = 19)中的蛋白质表达。生成了总体核和细胞质H评分,并研究了雄性和雌性以及不同解剖位置(轴位与附肢位)的核和细胞质评分,为了解这种癌症类型中的表达提供了独特机会。本研究有助于更深入地了解遗传途径变化,并确定人类和犬类骨肉瘤诊断、预后和治疗的途径,同时涵盖医学中的“同一个健康”概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/1a3ea97731b4/life-15-00951-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/0f03faf04dcb/life-15-00951-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/5741a1b8aca8/life-15-00951-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/82f6b44499d9/life-15-00951-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/ba0c451db1ad/life-15-00951-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/0a1ddd29d04e/life-15-00951-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/1a3ea97731b4/life-15-00951-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/0f03faf04dcb/life-15-00951-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/5741a1b8aca8/life-15-00951-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/82f6b44499d9/life-15-00951-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/ba0c451db1ad/life-15-00951-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/0a1ddd29d04e/life-15-00951-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d3/12194233/1a3ea97731b4/life-15-00951-g004.jpg

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本文引用的文献

1
Exploring circulating MiRNA signature for osteosarcoma detection: Bioinformatics-based analyzing and validation.探讨循环 miRNA 特征在骨肉瘤检测中的应用:基于生物信息学的分析和验证。
Pathol Res Pract. 2024 Nov;263:155615. doi: 10.1016/j.prp.2024.155615. Epub 2024 Oct 1.
2
Identification of a novel alternative splicing isoform of the Hippo kinase STK3/MST2 with impaired kinase and cell growth suppressing activities.鉴定 Hippo 激酶 STK3/MST2 的一种新型可变剪接异构体,其激酶和细胞生长抑制活性受损。
Oncogene. 2024 Sep;43(39):2938-2950. doi: 10.1038/s41388-024-03104-2. Epub 2024 Aug 22.
3
Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.
生物活性纳米复合水凝胶增强骨肉瘤治疗的术后免疫治疗和骨重建。
Biomaterials. 2025 Jan;312:122714. doi: 10.1016/j.biomaterials.2024.122714. Epub 2024 Jul 27.
4
Genomic Landscape of Osteosarcoma of Bone in an Older-Aged Patient Population and Analysis of Possible Etiologies Based on Molecular Signature.老年患者骨肉瘤的基因组图谱及基于分子特征的可能病因分析。
Genet Test Mol Biomarkers. 2024 Sep;28(9):351-359. doi: 10.1089/gtmb.2024.0080. Epub 2024 Jul 25.
5
The whole transcriptome analysis using FFPE and fresh tissue samples identifies the molecular fingerprint of osteosarcoma.使用 FFPE 和新鲜组织样本进行全转录组分析可确定骨肉瘤的分子特征。
Exp Biol Med (Maywood). 2024 Jun 20;249:10161. doi: 10.3389/ebm.2024.10161. eCollection 2024.
6
Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.抗体激活骨细胞缝隙连接半通道伴 ATP 释放抑制乳腺癌和骨肉瘤恶性进展。
Cell Rep. 2024 Jul 23;43(7):114377. doi: 10.1016/j.celrep.2024.114377. Epub 2024 Jun 17.
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Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma.犬骨肉瘤中FOXO4、IRF8和LEF1蛋白表达模式的免疫组织化学研究
Cancers (Basel). 2024 May 20;16(10):1945. doi: 10.3390/cancers16101945.
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