Background/Objectives: The response rate to immune checkpoint inhibitor (ICI) therapy is limited. Further, there is a need to discover biomarkers to predict therapeutic efficacy. The vascular endothelial growth factor (VEGF) is strongly associated with intra-tumoral immunity; however, its utility as a marker remains unknown. Therefore, our objectives were to examine the isoforms of VEGF and determine whether VEGF levels predict ICI efficacy. Methods: Levels of VEGF isoforms VEGF-A121 and VEGF-A165 were measured in stored serum samples obtained from 30 patients with advanced or recurrent gastric cancer who received nivolumab monotherapy at Kagoshima University Hospital, and the association with prognosis and treatment efficacy was retrospectively analyzed. Results: The serum levels of the total VEGF, VEGF-A121, and VEGF-A165 were not significantly associated with prognosis. However, the ratio of VEGF-A121/VEGF-A165 (VEGF-A121/165) exhibited a statistically significant (p= 0.0088) difference in progression-free survival (PFS) with the low-ratio group having a 67-day prolonged median PFS time. Under univariable analysis, only VEGF-A121/165 values exhibited reduced progression-free survival with statistical significance. When comparing treatment responses in the low (n= 15) and high(n= 15) serum VEGF-A-121/165 groups, RECIST evaluation was 3 to 0 for complete response (CR), 2 to 0 for partial response (PR), 3 to 2 for stable disease (SD), and 3 to 10 for progressive disease (PD). Patients with clinically unsettled PR or SD were classified as non-CR/non-PD (4 vs. 3), with a disease control rate of 80% vs. 33%. Conclusions: The serum VEGF-A121/165 ratio may represent a new, easily measured biomarker for predicting the therapeutic response to ICIs.
背景/目的：免疫检查点抑制剂（ICI）疗法的应答率有限，且亟需发现预测疗效的生物标志物。血管内皮生长因子（VEGF）与肿瘤内免疫密切相关，但其作为标志物的应用价值尚不明确。因此，本研究旨在检测VEGF亚型，并探究VEGF水平对ICI疗效的预测作用。方法：对鹿儿岛大学医院接受纳武利尤单抗单药治疗的30例晚期或复发性胃癌患者储存血清样本进行VEGF亚型（VEGF-A121与VEGF-A165）水平检测，回顾性分析其与预后及疗效的关联性。结果：血清总VEGF、VEGF-A121及VEGF-A165水平与预后无显著相关性。但VEGF-A121/165比值在无进展生存期（PFS）方面呈现统计学显著差异（p=0.0088），低比值组中位PFS延长67天。单变量分析显示，仅VEGF-A121/165比值与PFS缩短具有统计学显著性。比较低比值组（n=15）与高比值组（n=15）疗效时，RECIST评估显示完全缓解（CR）为3:0，部分缓解（PR）为2:0，疾病稳定（SD）为3:2，疾病进展（PD）为3:10。临床未确定的PR或SD患者归类为非CR/非PD（4:3），疾病控制率分别为80%与33%。结论：血清VEGF-A121/165比值可能成为预测ICI治疗反应的新型易测生物标志物。
肿瘤(癌症)患者之家