Ma Qiong, Sun Jin, Liu Qiao, Fu Jin, Wen Yanhua, Zhang Fuqin, Wu Yonghong, Zhang Xiaoyu, Gong Li, Zhang Wei
Department of Pathology, Tangdu Hospital, Air Force Medical University, 569 Xinsi Road, Xi'an 710038, China; Orthopedic Oncology Institute, Department of Orthopedic Surgery, Tangdu Hospital, Air Force Medical University, 569 Xinsi Road, Xi'an 710038, China.
Orthopedic Oncology Institute, Department of Orthopedic Surgery, Tangdu Hospital, Air Force Medical University, 569 Xinsi Road, Xi'an 710038, China.
Transl Oncol. 2024 Nov;49:102098. doi: 10.1016/j.tranon.2024.102098. Epub 2024 Aug 16.
Doxorubicin and cisplatin are both first-line chemotherapeutics for osteosarcoma (OS) treatment. However, the efficacy of doxorubicin/cisplatin chemotherapy varies considerably. Thus, identifying an efficient diagnostic biomarker to distinguish patients with good and poor responses to doxorubicin/cisplatin chemotherapy is of paramount importance.
To predict the efficacy of doxorubicin/cisplatin chemotherapy, we analyzed the differentially expressed proteins in 37 resected OS samples, which were categorized into the primary group (PG), the recurrent group (RG) and the metastatic group (MG). The characteristics of the enriched differentially expressed proteins were assessed via GO and KEGG analyses. Protein‒protein interactions were identified to determine the relationships among the differentially expressed proteins. Receiver operating characteristic (ROC) curve analyses were performed to explore the clinical significance of the differentially expressed proteins. Parallel reaction monitoring (PRM) was used to validate the candidate proteins. Immunohistochemical (IHC) staining was performed to confirm the expression of cathepsin (CTSG) in patients with good and poor response to doxorubicin/cisplatin.
A total of 9458 proteins were identified and quantified, among which 143 and 208 exhibited significant changes (|log2FC|>1, p < 0.05) in the RG and MG compared with the PG, respectively. GO and KEGG enrichment led to the identification of neutrophil extracellular traps (NETs). ROC curve analyses revealed 74 and 86 proteins with areas under the curve greater than 0.7 in the RG and MG, respectively. PRM validation revealed the statistical significance of CTSG, which is involved in NET formation, at the protein level in both the RG and MG. IHC staining of another cohort revealed that CTSG was prominently upregulated in the poor response group after treatment with doxorubicin/cisplatin.
CTSG and its associated NETs are potential biomarkers with which the efficacy of doxorubicin/cisplatin chemotherapy could be predicted in OS patients.
阿霉素和顺铂均为骨肉瘤（OS）治疗的一线化疗药物。然而，阿霉素/顺铂化疗的疗效差异很大。因此，识别一种有效的诊断生物标志物以区分对阿霉素/顺铂化疗反应良好和反应不佳的患者至关重要。
为预测阿霉素/顺铂化疗的疗效，我们分析了37例切除的OS样本中差异表达的蛋白质，这些样本分为原发组（PG）、复发组（RG）和转移组（MG）。通过GO和KEGG分析评估富集的差异表达蛋白质的特征。鉴定蛋白质-蛋白质相互作用以确定差异表达蛋白质之间的关系。进行受试者工作特征（ROC）曲线分析以探索差异表达蛋白质的临床意义。采用平行反应监测（PRM）验证候选蛋白质。进行免疫组织化学（IHC）染色以确认组织蛋白酶（CTSG）在对阿霉素/顺铂反应良好和反应不佳的患者中的表达。
共鉴定和定量了9458种蛋白质，其中与PG相比，RG和MG中分别有143种和208种蛋白质表现出显著变化（|log2FC|>1，p<0.05）。GO和KEGG富集分析鉴定出中性粒细胞胞外陷阱（NETs）。ROC曲线分析显示，RG和MG中分别有74种和86种蛋白质的曲线下面积大于0.7。PRM验证显示，参与NET形成的CTSG在RG和MG的蛋白质水平上具有统计学意义。另一队列的IHC染色显示，阿霉素/顺铂治疗后，反应不佳组中CTSG显著上调。
CTSG及其相关的NETs是潜在的生物标志物，可用于预测OS患者阿霉素/顺铂化疗的疗效。
