Torok Zsofia, Garai Kitti, Bovari-Biri Judit, Adam Zoltan, Miskei Judith A, Kajtar Bela, Sarosi Veronika, Pongracz Judit E
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, 2 Rokus Str, Pecs, Pecs, H-7624, Hungary.
Department of Pulmonology, 1st Internal Medicine, The Medical School and Clinical Centre, University of Pecs, 12 Szigeti Str, Pecs, H-7624, Hungary.
Respir Res. 2025 Apr 13;26(1):141. doi: 10.1186/s12931-025-03216-7.
Despite significant advances in the treatment of lung cancer (LC), there are no reliable biomarkers to effectively predict therapy response and overall survival (O/S) in non-small cell lung cancer (NSCLC) subtypes. While targeted therapies have improved survival rates in lung adenocarcinoma (LUAD), effective treatment options for lung squamous cell carcinoma (LUSC) are still limited. Recent evidence indicates that exosome-bound WNT5A may significantly contribute to disease progression. Our study assessed the WNT5A protein as a potential biomarker for diagnosing patients and predicting prognosis to assist in therapy selection.
Primary tumor tissue and serum samples were collected from a cohort of 60 patients with histologically confirmed NSCLC before therapy. Healthy serum donors served as controls. Exosomes were isolated, then exosome number and size were measured, and WNT5A protein levels were identified in tissue and in vesicle-free, vesicle-bound fractions of the serum by ELISA.
Extensive statistical analysis (ROC, AUC, Cox, etc.) revealed that elevated WNT5A levels on the serum-exosome surface correlated with distant metastasis, advanced disease stage, and lymph node involvement in LUSC but not in LUAD patients. Moreover, a high WNT5A exosome surface expression was associated with a poor response to therapy and shorter O/S in LUSC patients. Additionally, serum-exosome surface + cargo WNT5A content distinguished LUAD and LUSC subtypes.
WNT5A, particularly its serum exosome-bound form, may serve as a valuable biomarker after further validation for differentiating NSCLC subtypes and predicting disease progression. Importantly, the information can become available from a simple serum sample at the time of diagnosis.
尽管肺癌（LC）治疗取得了显著进展，但在非小细胞肺癌（NSCLC）亚型中，仍没有可靠的生物标志物来有效预测治疗反应和总生存期（O/S）。虽然靶向治疗提高了肺腺癌（LUAD）的生存率，但肺鳞状细胞癌（LUSC）的有效治疗选择仍然有限。最近的证据表明，外泌体结合的WNT5A可能对疾病进展有显著影响。我们的研究评估了WNT5A蛋白作为诊断患者和预测预后以辅助治疗选择的潜在生物标志物。
从60例经组织学确诊的NSCLC患者队列中收集治疗前的原发性肿瘤组织和血清样本。健康血清捐赠者作为对照。分离外泌体，然后测量外泌体数量和大小，并通过ELISA在组织以及血清的无囊泡、结合囊泡部分中鉴定WNT5A蛋白水平。
广泛的统计分析（ROC、AUC、Cox等）显示，血清外泌体表面WNT5A水平升高与LUSC患者的远处转移、疾病晚期和淋巴结受累相关，但与LUAD患者无关。此外，高WNT5A外泌体表面表达与LUSC患者对治疗的不良反应和较短的O/S相关。此外，血清外泌体表面+货物WNT5A含量可区分LUAD和LUSC亚型。
WNT5A，特别是其血清外泌体结合形式，在进一步验证后可能作为区分NSCLC亚型和预测疾病进展的有价值生物标志物。重要的是，在诊断时可从简单的血清样本中获得该信息。
