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小细胞肺癌中PDL1和DLL3生物标志物的表达模式及临床意义:回顾性研究:对治疗策略和生存预测的见解

Expression patterns and clinical implications of PDL1 and DLL3 biomarkers in small cell lung cancer retrospectively studied: Insights for therapeutic strategies and survival prediction.

作者信息

Domvri Kalliopi, Yaremenko Alexey V, Apostolopoulos Apostolos, Petanidis Savvas, Karachrysafi Sofia, Pastelli Nikoleta, Papamitsou Theodora, Papaemmanouil Styliani, Lampaki Sofia, Porpodis Konstantinos

机构信息

Laboratory of Histology-Embryology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Pathology Department, George Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

Heliyon. 2024 Feb 29;10(5):e27208. doi: 10.1016/j.heliyon.2024.e27208. eCollection 2024 Mar 15.

Abstract

Lung cancer is a leading cause of cancer-related deaths globally, includes small cell lung cancer (SCLC), characterized by its aggressive nature and advanced disease at diagnosis. However, the identification of reliable biomarkers for SCLC has proven challenging, as no consistent predictive biomarker has been established. Nonetheless, certain tumor-associated antigens, including programmed death-ligand 1 (PDL1) and Delta-Like Ligand 3 (DLL3), show promise for targeted antibody-based immunotherapy. To ensure optimal patient selection, it remains crucial to comprehend the relationship between PDL1 and DLL3 expression and clinicopathological characteristics in SCLC. In this study, we investigated the expression patterns of PDL1 and DLL3 biomarkers in endobronchial samples from 44 SCLC patients, examining their association with clinical characteristics and survival. High PDL1 expression (>1%) was observed in 14% of patients, while the majority the SCLC patients (73%) exhibited high DLL3 expression (>75%). Notably, we found a positive correlation between high PDL1 expression (>1%) and overall survival. However, we did not observe any significant differences in the biomarkers expression concerning age, sex, disease status, smoking status, or distant metastases. Further subgroup analysis revealed that a high co-expression of both PDL1 (>1%) and DLL3 (100%) antigens was associated with improved overall survival. This suggests that SCLC expressing PDL1 and DLL3 antigens may exhibit increased sensitivity to therapy, indicating their potential as therapeutic targets. Thus, our findings provide novel insights into the simultaneous evaluation of PDL1 and DLL3 biomarkers in SCLC patients. These insights have significant clinical implications for therapeutic strategies, survival prediction, and development of combination immunotherapies.

摘要

肺癌是全球癌症相关死亡的主要原因,包括小细胞肺癌(SCLC),其特点是具有侵袭性且在诊断时病情已发展到晚期。然而,事实证明,识别SCLC可靠的生物标志物具有挑战性,因为尚未建立一致的预测性生物标志物。尽管如此,某些肿瘤相关抗原,包括程序性死亡配体1(PDL1)和Delta样配体3(DLL3),在基于抗体的靶向免疫治疗方面显示出前景。为确保最佳的患者选择,了解PDL1和DLL3表达与SCLC临床病理特征之间的关系仍然至关重要。在本研究中,我们调查了44例SCLC患者支气管内样本中PDL1和DLL3生物标志物的表达模式,研究它们与临床特征和生存的相关性。14%的患者观察到高PDL1表达(>1%),而大多数SCLC患者(73%)表现出高DLL3表达(>75%)。值得注意的是,我们发现高PDL1表达(>1%)与总生存期呈正相关。然而,我们未观察到生物标志物表达在年龄、性别、疾病状态、吸烟状态或远处转移方面存在任何显著差异。进一步的亚组分析显示,PDL1(>1%)和DLL3(100%)抗原的高共表达与总生存期改善相关。这表明表达PDL1和DLL3抗原的SCLC可能对治疗表现出更高的敏感性,表明它们作为治疗靶点的潜力。因此,我们的研究结果为同时评估SCLC患者的PDL1和DLL3生物标志物提供了新的见解。这些见解对治疗策略、生存预测和联合免疫治疗的发展具有重要的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a8/10926129/7d4575f87fea/gr1.jpg

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