Liang Mengjie, Lu Junren, Wang Xingzhou, Song Peng, Ai Shichao, Cai Daming, Sun Feng, Lu Xiaofeng, Wang Meng, Fu Shuang, Yu Heng, Guan Wenxian, Shen Xiaofei
Department of General Surgery, Division of Gastric Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University , Nanjing, China.
Department of Anesthesiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Clin Transl Gastroenterol. 2025 Apr 4;16(6):e00842. doi: 10.14309/ctg.0000000000000842. eCollection 2025 Jun 1.
Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach tumor. However, limited data exist about the expression and clinical significance of B7 family ligands/receptors in patients with g-NENs. Thus, we conducted this study to address this issue in a cohort of 112 patients with g-NENs.
Using immunohistochemistry, we mapped and quantified the expression of the B7 family ligands/receptors in 112 g-NEN samples: programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), B7-H3, B7-H4, recombinant human galectin-9 (LGALS9), and CD155. Associations between the marker levels, clinicopathological variables, and survival were evaluated.
The percentages of high expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 in the cohort of 112 g-NEN cases were 37.5%, 55.4%, 46.4%, 37.5%, 46.4%, and 51.8%, respectively. Elevated expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 was significantly associated with several clinicopathological characteristics. K-M analysis indicated that high expression levels of CD155, B7-H3, PD-L2, and LGALS9 were correlated with poor overall survival (OS) ( P < 0.0001, P = 0.0002, P = 0.0319 and P = 0.0120, respectively). Multivariate Cox regression analysis indicated that high CD155 expression, vasculature invasion, and worse World Health Organization pathological grade were independent prognostic factors for OS ( P = 0.007, P = 0.030, and P = 0.019, respectively).
We detected variable expression of the PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins in g-NENs. These results suggest that the expression level of CD155 may be a vital indicator of OS in patients with g-NENs. B7 family ligands/receptors could be potential immunotherapeutic targets for g-NENs.
胃神经内分泌肿瘤（g-NENs）是一种罕见的胃部肿瘤。然而，关于g-NENs患者中B7家族配体/受体的表达及临床意义的数据有限。因此，我们开展了这项研究，以在112例g-NENs患者队列中解决这一问题。
我们采用免疫组织化学方法，对112例g-NENs样本中B7家族配体/受体的表达进行定位和定量分析，这些配体/受体包括程序性细胞死亡配体1和2（PD-L1和PD-L2）、B7-H3、B7-H4、重组人半乳糖凝集素-9（LGALS9）和CD155。评估了标志物水平、临床病理变量与生存率之间的关联。
在112例g-NENs病例队列中，PD-L1、PD-L2、B7-H3、B7-H4、LGALS9和CD155高表达的百分比分别为37.5%、55.4%、46.4%、37.5%、46.4%和51.8%。PD-L1、PD-L2、B7-H3、B7-H4、LGALS9和CD-155的表达升高与多种临床病理特征显著相关。K-M分析表明，CD155、B7-H3、PD-L2和LGALS9的高表达水平与总生存期（OS）较差相关（分别为P < 0.0001、P = 0.0002、P = 0.0319和P = 0.0120）。多变量Cox回归分析表明，CD155高表达、脉管浸润和世界卫生组织病理分级较差是OS的独立预后因素（分别为P = 0.007、P = 0.030和P = 0.019）。
我们在g-NENs中检测到PD-L1、PD-L2、B7-H3、B7-H4、LGALS9和CD15蛋白的表达存在差异。这些结果表明，CD155的表达水平可能是g-NENs患者OS的重要指标,B7家族配体/受体可能是g-NENs潜在的免疫治疗靶点。
