中期因子表达作为预测IA期肺腺癌复发的候选生物标志物
Midkine Expression as a Candidate Biomarker to Predict the Recurrence of Stage IA Lung Adenocarcinoma.
作者信息
Yang Xiao, Sun Shuo, Kuang Xunjie, Lu Xianfeng, Xiao He, Duan Yi, Xiong Yanli, Zhang Di, Xu Yu, Zhu Jianwu, Li Mengxia
机构信息
Department of Cancer Center, Army Medical Center of People's Liberation Army (PLA), Chongqing, People's Republic of China.
出版信息
JTO Clin Res Rep. 2025 Jun 13;6(9):100858. doi: 10.1016/j.jtocrr.2025.100858. eCollection 2025 Sep.
BACKGROUND
Early recurrence limits the long-term survival of postoperative patients with stage IA lung adenocarcinoma (LUAD). This study aims to risk-stratify postoperative stage IA LUAD by means of the expression of Midkine (MDK).
MATERIALS AND METHODS
We collected surgical samples from 62 patients with stage IA LUAD, of which 30 patients had early recurrence and others without. Intratumoral and peritumoral MDK expression were measured by immunohistochemistry staining. We also analyzed the MDK expression of stage IA LUAD from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus repository.
RESULTS
The intratumoral MDK was significantly overexpressed in patients with early recurrence ( < 0.001). Kaplan-Meier survival analysis revealed that patients with higher intratumoral MDK expression had poor recurrence-free survival ( < 0.001) and overall survival ( = 0.004). Univariate Cox regression analysis indicated that intratumoral MDK expression significantly increased the risk of recurrence (hazard ratio [HR] 1.408 (1.076-1.842), = 0.013) and death (HR 1.888 [1.127-3.162], = 0.016). Stepwise Cox regression analysis revealed that smoking (HR 2.944 [1.419-6.107], = 0.004), intratumoral MDK expression (HR 1.316 [1.037-1.669], = 0.024), and mutation (HR 2.407 [1.110-5.221], = 0.026) were independent prognostic factors for early recurrence. In TCGA data set, the MDK expression significantly increased the risk of recurrence (HR 1.559 [1.035-2.349], = 0.034), and patients with higher MDK expression had worse disease-free survival ( = 0.024). In GSE31210, the MDK expression significantly increased the risk of recurrence (HR 2.617 [1.791-3.824], < 0.001) and death (HR 2.495 [1.429-4.356], = 0.001), whereas patients with higher MDK expression also had worse recurrence-free survival ( = 0.006) and overall survival ( < 0.001).
CONCLUSION
MDK was considered a putative candidate for predicting early recurrence in patients with stage IA LUAD.
背景
早期复发限制了IA期肺腺癌（LUAD）术后患者的长期生存。本研究旨在通过中期因子（MDK）的表达对术后IA期LUAD进行风险分层。
材料与方法
我们收集了62例IA期LUAD患者的手术样本，其中30例患者出现早期复发，其余患者未复发。通过免疫组织化学染色测量肿瘤内和肿瘤周围的MDK表达。我们还分析了来自癌症基因组图谱（TCGA）和基因表达综合数据库中IA期LUAD的MDK表达。
结果
肿瘤内MDK在早期复发患者中显著过表达（<0.001）。Kaplan-Meier生存分析显示，肿瘤内MDK表达较高的患者无复发生存期较差（<0.001）和总生存期较差（=0.004）。单因素Cox回归分析表明，肿瘤内MDK表达显著增加复发风险（风险比[HR]1.408[1.076 - 1.842]，=0.013）和死亡风险（HR 1.888[1.127 - 3.162]，=0.016）。逐步Cox回归分析显示，吸烟（HR 2.944[1.419 - 6.107]，=0.004）、肿瘤内MDK表达（HR 1.316[1.037 - 1.669]，=0.024）和 突变（HR 2.407[1.110 - 5.221]，=0.026）是早期复发的独立预后因素。在TCGA数据集中，MDK表达显著增加复发风险（HR 1.559[1.035 - 2.349]，=0.034），且MDK表达较高的患者无病生存期较差（=0.024）。在GSE31210中，MDK表达显著增加复发风险（HR 2.617[1.791 - 3.824]，<0.001）和死亡风险（HR 2.495[1.429 - 4.356]，=0.001），而MDK表达较高的患者无复发生存期也较差（=0.006）和总生存期较差（<0.001）。
结论
MDK被认为是预测IA期LUAD患者早期复发的一个假定候选指标。
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