Potential of VEGFR2 expression as a predictive marker of PD-1 blockade in patients with advanced NSCLC
Potential of VEGFR2 expression as a predictive marker of PD-1 blockade in patients with advanced NSCLC
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DOI：
10.3892/or.2022.8429
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发表时间：
2022-12-01
期刊：
影响因子：
4.2
通讯作者：
Kagamu, Hiroshi
中科院分区：
文献类型：
--
作者：
Kaira, Kyoichi;Imai, Hisao;Kagamu, Hiroshi
血管生成在癌症进展中起着至关重要的作用。血管内皮生长因子（VEGF）在癌症患者中表现出免疫抑制功能。然而，目前尚不清楚肿瘤组织中VEGF的表达是否可以预测晚期非小细胞肺癌（NSCLC）患者中程序性死亡-1阻断的结果。入组接受一线帕博利珠单抗治疗的晚期NSCLC患者的培训（n=32）和验证（n=76）队列。在两个队列的肿瘤标本中进行VEGF受体2（VEGFR 2）和肿瘤浸润淋巴细胞（TIL; CD 4、CD 8和FOXP 3）的免疫组织化学染色，并评估与临床结局的相关性。VEGFR 2高表达的百分比在训练队列中为34.3%（11/32），在验证队列中为25.0%（19/76）。在训练（27.2 vs. 45.0%）和验证（31.2 vs. 35.7%）队列中，未观察到高和低VEGFR 2表达之间客观缓解的统计学显著差异。对于验证队列，肿瘤内FOXP 3的阳性率与VEGFR 2的高表达显著相关，但对于训练队列，FOXP 3的阳性率与VEGFR 2的高表达无关。在验证队列中，非腺癌（非AC）患者的高VEGFR 2表达与肿瘤内和间质部位的阳性FOXP 3 TIL显著相关，但与CD 4和CD 8无关。两个队列中的高VEGFR 2表达表明总生存期（OS）比低VEGFR 2表达显著更差。VEGFR 2被确定为与OS恶化相关的独立预后标志物。VEGFR 2高表达是预测一线帕博利珠单抗治疗患者OS恶化的重要标志物，特别是非AC患者。
Angiogenesis serves a crucial role in cancer progression. Vascular endothelial growth factor (VEGF) exhibits an immunosuppressive function in patients with cancer. However, it remains unclear whether expression of VEGF in tumor tissue can predict the outcome of programmed death-1 blockade in patients with advanced non-small cell lung cancer (NSCLC). A training (n=32) and validation (n=76) cohort of patients with advanced NSCLC who received first-line pembrolizumab were enrolled. Immunohistochemical staining for VEGF receptor 2 (VEGFR2) and tumor-infiltrating lymphocytes (TILs; CD4, CD8 and FOXP3) was performed in tumor specimens of both cohorts and association with clinical outcomes was assessed. The percentages of high VEGFR2 expression were 34.3% (11/32) in training cohort and 25.0% (19/76) in validation cohort. No statistically significant difference in objective response between high and low VEGFR2 expression was observed for training (27.2 vs. 45.0%) and validation (31.2 vs. 35.7%) cohorts. The positive rate of intratumoral FOXP3 was significantly associated with high VEGFR2 expression for validation cohort, but not training cohort. In validation cohort, high VEGFR2 expression in patients with non-adenocarcinoma (non-AC) was significantly correlated with positive FOXP3 TILs in intratumoral and stromal sites, but not CD4 and CD8. High VEGFR2 expression in both cohorts indicated a significantly worse overall survival (OS) than low VEGFR2 expression. VEGFR2 was identified as an independent prognostic marker associated with worse OS. High VEGFR2 expression was a significant marker for predicting worse OS in patients treated with first-line pembrolizumab, particularly in those with non-AC.