Hamada Yuki, Tanoue Kiyonori, Arigami Takaaki, Yamakuchi Munekazu, Okawa Masashi, Matsushita Daisuke, Takenouchi Kazunori, Yamada Shingo, Maywar Drew N, Nakayama Chieri, Oyama Yoko, Higashi Sadayuki, Fujisaki Chieko, Hozaka Yuto, Kita Yoshiaki, Hashiguchi Teruto, Ohtsuka Takao
Department of Digestive Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Cancers (Basel). 2024 Nov 26;16(23):3958. doi: 10.3390/cancers16233958.
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.
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.
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 ( = 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 ( = 15) and high = 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%.
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）治疗的有效率有限。此外，需要发现预测治疗效果的生物标志物。血管内皮生长因子（VEGF）与肿瘤内免疫密切相关；然而，其作为标志物的效用尚不清楚。因此，我们的目的是检测VEGF的异构体，并确定VEGF水平是否能预测ICI疗效。
在鹿儿岛大学医院接受纳武单抗单药治疗的30例晚期或复发性胃癌患者的储存血清样本中，检测VEGF异构体VEGF-A121和VEGF-A165的水平，并回顾性分析其与预后和治疗效果的相关性。
VEGF、VEGF-A121和VEGF-A165的血清水平与预后无显著相关性。然而，VEGF-A121/VEGF-A165（VEGF-A121/165）比值在无进展生存期（PFS）上显示出统计学显著差异（P = 0.0088），低比值组的中位PFS时间延长了67天。在单变量分析中，只有VEGF-A121/165值显示出无进展生存期缩短且具有统计学意义。比较血清VEGF-A-121/165低（n = 15）高（n = 15）组的治疗反应时，根据实体瘤疗效评价标准（RECIST）评估，完全缓解（CR）为3至0，部分缓解（PR）为2至0，疾病稳定（SD）为3至2，疾病进展（PD）为3至10。临床PR或SD未明确的患者归类为非CR/非PD（4例对3例），疾病控制率分别为80%和33%。
血清VEGF-A121/165比值可能代表一种新的、易于检测的预测ICI治疗反应的生物标志物。
