Miyamoto Tatsuya, Haruki Tomohiro, Makishima Karen, Matsui Shinji, Oshima Yuki, Umekita Yoshihisa, Nakamura Hiroshige
Department of Surgery, Division of General Thoracic Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
Department of Pathology, Division of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
Thorac Cancer. 2024 Dec;15(36):2519-2529. doi: 10.1111/1759-7714.15477. Epub 2024 Nov 2.
Podoplanin (PDPN) expression in cancer-associated fibroblasts (CAFs) (CAF-PDPN) is considered a poor prognostic factor in nonsmall cell lung cancer, but little is known about its clinical significance in high-grade neuroendocrine carcinoma of the lung (HGNEC). This study examines the association between CAF-PDPN and stromal programmed death-ligand 1 (PD-L1) expression and the prognostic implications of CAF-PDPN and PD-L1 expression status in surgically resected HGNEC patients.
Immunohistochemical analyses were performed on 121 resected HGNEC specimens using antibodies against PDPN and PD-L1. Correlations between CAF-PDPN, stromal PD-L1 expression, and clinicopathologic features and their implications for survival were analyzed statistically.
There were substantially more large-cell neuroendocrine carcinomas in the stromal PD-L1-positive group and more vascular invasion in the tumoral PD-L1-positive group. PDPN expression in CAF was moderately correlated with stromal PD-L1 expression (ρ = 0.567, p < 0.001). In a survival analysis combining CAF-PDPN and stromal PD-L1 status, the 5-year RFS rates for Group A: CAF-PDPN (+)/stromal PD-L1 (+), Group B: CAF-PDPN (+)/stromal PD-L1 (-), Group C: CAF-PDPN (-)/stromal PD-L1 (+), and Group D: CAF-PDPN (-)/stromal PD-L1 (-) were 62.0%, 46.8%, 17.5%, and 20.2%, respectively, with corresponding 5-year OS rates of 76.6%, 69.2%, 27.0%, and 25.3%. The log-rank test showed statistically significant differences among the groups in RFS (p < 0.001) and OS (p < 0.001).
There is a correlation between CAF-PDPN and tumoral/stromal PD-L1 expression, and positive status for either CAF-PDPN or stromal PD-L1 expression could be an independent favorable prognostic factor in surgically resected HGNEC patients.
在非小细胞肺癌中，癌相关成纤维细胞（CAF）中血小板源性生长因子受体β（PDPN）的表达被认为是一个不良预后因素，但关于其在肺高级别神经内分泌癌（HGNEC）中的临床意义知之甚少。本研究探讨CAF-PDPN与基质程序性死亡配体1（PD-L1）表达之间的关联，以及CAF-PDPN和PD-L1表达状态对手术切除的HGNEC患者的预后影响。
使用抗PDPN和PD-L1抗体对121例切除的HGNEC标本进行免疫组织化学分析。对CAF-PDPN、基质PD-L1表达与临床病理特征之间的相关性及其对生存的影响进行统计学分析。
基质PD-L1阳性组中，大细胞神经内分泌癌显著更多；肿瘤PD-L1阳性组中，血管侵犯更多。CAF中PDPN表达与基质PD-L1表达呈中度相关（ρ = 0.567，p < 0.001）。在结合CAF-PDPN和基质PD-L1状态的生存分析中，A组（CAF-PDPN(+)/基质PD-L1(+)）、B组（CAF-PDPN(+)/基质PD-L1(-)）、C组（CAF-PDPN(-)/基质PD-L1(+)）和D组（CAF-PDPN(-)/基质PD-L1(-)）的5年无复发生存率分别为62.0%、46.8%、17.5%和20.2%，相应的5年总生存率分别为76.6%、69.2%、27.0%和25.3%。对数秩检验显示，各组间无复发生存率（p < 0.001）和总生存率（p < 0.001）存在统计学显著差异。
CAF-PDPN与肿瘤/基质PD-L1表达之间存在相关性，CAF-PDPN或基质PD-L1表达阳性可能是手术切除的HGNEC患者的一个独立有利预后因素。
