Vanderheijden Cas, Yakkioui Youssef, Vaessen Thomas, Santegoeds Remco, Temel Yasin, Hoogland Govert, Hovinga Koos
Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands.
School of Mental Health and Neuroscience, Experimental Neurosurgery, Maastricht University, Maastricht, The Netherlands.
J Neurooncol. 2025 Mar;172(1):249-256. doi: 10.1007/s11060-024-04913-x. Epub 2024 Dec 17.
Chordomas are malignant tumors of the axial spine and skull base, and they are notorious for their poor treatment response. Differentiating these tumors from comparatively less malignant chondrosarcomas is crucial for treatment and prognostication. Both tumor types differ in their developmental origin. Chordomas are considered to be derived from notochordal remnants and chondrosarcomas from mesenchymal cells. Here, we evaluated the differential expression of developmental transcription factors in these skull base tumors.
Histopathologically-confirmed tumor biopsies were obtained from 12 chordoma and 7 chondrosarcoma patients. Following RNA extraction, samples were submitted to real-time quantitative PCR (RT-qPCR) for the evaluation of 32 evolutionary conserved genes that are known to associate with notochord, mesoderm, and axial spine development. Gene expression levels were normalized to housekeeping genes ACTB and RS27a.
Fifteen genes were either exclusively expressed (n = 12) or overexpressed (n = 3; 2.21-4.43 fold increase) in chordoma, compared to chondrosarcoma. Brachyury and CD24 were highly and exclusively expressed in chordoma. Other novel genes exclusive to chordomas included chordin, HOXA5 and ACAN. Vice versa, ten genes were either exclusively expressed (n = 2) or overexpressed (n = 8; 0.01-0.66 fold increase) in chondrosarcoma, compared to chordoma.
As chordoma patients demonstrate a worse prognosis compared to chondrosarcoma patients, the differential expression of chordin, HOXA5 and ACAN and CD24 could be relevant for the pathophysiology of chordomas and may have diagnostic and treatment value. Further study on role of these genes in tumorigenesis is therefore warranted.
脊索瘤是脊柱和颅底的恶性肿瘤，其治疗反应不佳，声名狼藉。将这些肿瘤与恶性程度相对较低的软骨肉瘤区分开来对治疗和预后至关重要。这两种肿瘤类型在发育起源上有所不同。脊索瘤被认为起源于脊索残余，而软骨肉瘤起源于间充质细胞。在此，我们评估了这些颅底肿瘤中发育转录因子的差异表达。
从12例脊索瘤患者和7例软骨肉瘤患者中获取经组织病理学证实的肿瘤活检样本。提取RNA后，将样本进行实时定量PCR（RT-qPCR），以评估32个与脊索、中胚层和脊柱发育相关的进化保守基因。基因表达水平以管家基因ACTB和RS27a进行标准化。
与软骨肉瘤相比，15个基因在脊索瘤中要么特异性表达（n = 12），要么过度表达（n = 3；增加2.21 - 4.43倍）。Brachyury和CD24在脊索瘤中高度且特异性表达。其他脊索瘤特有的新基因包括脊索蛋白、HOXA5和ACAN。反之，与脊索瘤相比，10个基因在软骨肉瘤中要么特异性表达（n = 2），要么过度表达（n = 8；增加0.01 - 0.66倍）。
由于脊索瘤患者的预后比软骨肉瘤患者更差，脊索蛋白、HOXA5、ACAN和CD24的差异表达可能与脊索瘤的病理生理学相关，并且可能具有诊断和治疗价值。因此，有必要进一步研究这些基因在肿瘤发生中的作用。
