肺腺癌中磷酸化Axl受体的脱落：双结构域免疫组织化学方法

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-08-07 DOI:10.1016/j.jtocrr.2025.100889

Shuji Mishima MD , Takashi Eguchi MD PhD , Yoshinori Sato MD , Shunichiro Matsuoka MD, PhD , Yuichi Oguchi MD , Mari Katsuno MD , Daisuke Nakamura MD , Yukihiro Terada MD , Hirotaka Kumeda MD , Kentaro Miura MD, PhD , Kazutoshi Hamanaka MD, PhD , Mai Iwaya MD, PhD , Takeshi Uehara MD, PhD , Kimihiro Shimizu MD, PhD

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引用次数: 0

摘要

axl是一种酪氨酸激酶受体，与上皮-间质转化（EMT）有关。本研究旨在探讨肺腺癌中磷酸化Axl （pAxl）细胞外结构域脱落的生物学意义，重点关注作为EMT潜在病理表征的通过空气间隙扩散（STAS）。方法本研究纳入202例肺腺癌切除术患者。采用双结构域免疫组化方法，分别对细胞外和细胞内结构域进行染色，将肿瘤分为脱落和非脱落pAxl组。以无复发概率（RFP）作为主要预后指标进行预后分析。此外，通过使用公共基因数据库，我们开发了“脱落pAxl评分”，以实验研究emt相关基因的相关性。结果pAxl脱落组预后明显差于非pAxl脱落组（5年RFP分别为54%和80%；p < 0.001）。这种pAxl脱落的预后分层在stas阳性患者中占主导地位（5年RFP分别为37%和75%，p < 0.001），但在stas阴性患者中不占主导地位（5年RFP分别为73%和84%，p = 0.3）。多因素分析显示，病理分期和pAxl脱落是复发的独立因素（危险比2.28 [1.24-4.91],p = 0.008）。脱落pAxl评分与建立的EMT特征评分密切相关（p < 0.001, R = 0.61）。结论pAxl脱落对肺腺癌的预后有影响，且与STAS相关的效应改变显著。已开发的pAxl脱落评分与EMT密切相关，为进一步研究这种现象在肺癌进展中的作用提供了基础知识。

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Shedding Phosphorylated Axl Receptor in Lung Adenocarcinoma: Dual-Domain Immunohistochemistry Approach

Introduction

Axl, a receptor tyrosine kinase, is linked to epithelial-mesenchymal transition (EMT). This study aimed to investigate the biologic implications of extracellular domain shedding of phosphorylated Axl (pAxl) in lung adenocarcinoma, focusing on spread through air spaces (STAS) as a potential pathologic representation of EMT.

Methods

This study included 202 patients with resected lung adenocarcinoma. A dual-domain immunohistochemistry approach using separate staining for the extracellular and intracellular domains was used to classify the tumors into shedding and nonshedding pAxl groups. Prognostic analysis was performed using recurrence-free probability (RFP) as the primary outcome. Furthermore, by using a public gene database, we developed the “shedding pAxl score” to experimentally investigate correlations with EMT-related genes.

Results

The shedding pAxl group exhibited significantly worse prognosis than the nonshedding pAxl group (5-year RFP, 54% and 80%, respectively; p < 0.001). This prognostic stratification of pAxl shedding was predominant in STAS-positive patients (5-year RFP, 37% and 75%, p < 0.001), but not in STAS-negative patients (5-year RFP, 73% and 84%, p = 0.3). Multivariate analysis revealed that pathologic stage and pAxl shedding were independent factors for recurrence (hazard ratio 2.28 [1.24–4.91], p = 0.008). The shedding pAxl score correlated strongly with the established EMT signature score (p < 0.001, R = 0.61).

Conclusions

Shedding pAxl has a prognostic impact on lung adenocarcinoma, with a significant effect modification related to STAS. The developed shedding pAxl score, strongly associated with EMT, provides foundational knowledge for further studies on this phenomenon in lung cancer progression.

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