Khalil Elzahraa Ibrahim Mohamed, Mohamed Fatma El Zahraa Ammar, Kamal Mohamed Rehab
Pathology Department, Faculty of Medicine, Minia University, Minia, Egypt.
Pathological Sciences Department, MBBS Program,, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.
J Egypt Natl Canc Inst. 2025 Apr 25;37(1):24. doi: 10.1186/s43046-025-00269-z.
Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Between 35 and 45% of these patients do not respond to standard chemotherapeutic treatments, resulting in a very low 5-year survival rate of only 5-20%. This resistance often leads to treatment failure and unfavorable prognoses, highlighting the critical need for new therapeutic targets to improve treatment strategies. Autophagy-related gene 4 B (ATG4B) is a crucial cysteine protease for autophagosome formation. It is overexpressed and correlates with poor prognosis in various cancers. However, the relationship between ATG4B expression and angiogenesis in OS remains unexplored. This study investigated the expression levels of ATG4B and VEGF in OS and their correlation with clinicopathological data.
This study included 67 paraffin-embedded OS tissue samples. ATG4B and VEGF expression levels were assessed via immunohistochemistry, and their associations with clinicopathological variables were statistically analyzed. Additionally, ATG4B gene expression in OS was examined via GEO datasets from https://www.ncbi.nlm.nih.gov .
ATG4B and VEGF were expressed in 79.1% and 74.6% of the osteosarcoma samples, respectively. There was a significant positive correlation between ATG4B expression and tumor size, tumor stage, and histological response to neoadjuvant chemotherapy, with p values of 0.013, 0.008, and 0.022, respectively. VEGF expression was also significantly correlated with tumor size, tumor stage, and the presence of distant metastasis at diagnosis, with p values of 0.022, 0.044, and 0.013, respectively. A notable positive correlation between ATG4B and VEGF expression levels was observed (p=0.002), which was supported by the GEO dataset analysis. High ATG4B and VEGF overexpression were significantly associated with worse overall survival by univariate analysis.
The results suggest that ATG4B acts as a tumor promoter in OS, indicating its potential as a therapeutic target to inhibit tumor growth. Elevated ATG4B levels may also serve as a marker for poor prognosis. Additionally, VEGF overexpression is linked to a greater likelihood of pulmonary metastasis and a worse overall prognosis. The positive correlation between ATG4B and VEGF suggests that the absence of both markers could be indicative of a better chemotherapy response, offering insights into potential new treatment approaches.
骨肉瘤（OS）是儿童和青少年中最常见的原发性骨癌。这些患者中有35%至45%对标准化疗治疗无反应，导致极低的5年生存率，仅为5%至20%。这种耐药性常常导致治疗失败和不良预后，凸显了对新治疗靶点的迫切需求，以改善治疗策略。自噬相关基因4B（ATG4B）是自噬体形成的关键半胱氨酸蛋白酶。它在各种癌症中过度表达且与预后不良相关。然而，OS中ATG4B表达与血管生成之间的关系仍未得到探索。本研究调查了OS中ATG4B和VEGF的表达水平及其与临床病理数据的相关性。
本研究纳入67例石蜡包埋的OS组织样本。通过免疫组织化学评估ATG4B和VEGF的表达水平，并对它们与临床病理变量的关联进行统计学分析。此外，通过来自https://www.ncbi.nlm.nih.gov的GEO数据集检测OS中ATG4B基因的表达。
ATG4B和VEGF分别在79.1%和74.6%的骨肉瘤样本中表达。ATG4B表达与肿瘤大小、肿瘤分期以及对新辅助化疗的组织学反应之间存在显著正相关，p值分别为0.013、0.008和0.022。VEGF表达也与肿瘤大小、肿瘤分期以及诊断时远处转移的存在显著相关，p值分别为0.022、0.044和0.013。观察到ATG4B和VEGF表达水平之间存在显著正相关（p = 0.002），这得到了GEO数据集分析的支持。单因素分析显示，ATG4B和VEGF高表达与较差的总生存期显著相关。
结果表明，ATG4B在OS中起肿瘤促进作用，表明其作为抑制肿瘤生长的治疗靶点的潜力。ATG4B水平升高也可能作为预后不良的标志物。此外，VEGF过表达与肺转移的可能性增加和总体预后较差有关。ATG4B和VEGF之间的正相关表明，两者标志物的缺失可能预示着更好的化疗反应，为潜在的新治疗方法提供了见解。
