Expression Patterns of Immune Checkpoint Molecules and Their Clinical Values in Gastric Neuroendocrine Neoplasms

Q: Which immune checkpoint molecules were evaluated in gastric neuroendocrine neoplasms?

The study quantified PD-L1, PD-L2, B7-H3, B7-H4, LGALS9 (galectin-9), and CD155 in 112 g-NEN samples using immunohistochemistry.

Q: How were the marker levels related to clinicopathological features?

Elevated expression of the studied markers was significantly associated with several clinicopathological characteristics across the cohort.

Q: Which factors were independent predictors of overall survival?

Multivariate Cox regression indicated high CD155 expression, vasculature invasion, and worse World Health Organization pathological grade as independent prognostic factors for overall survival.

Sep 23, 2026

Uploaded by Quinn Holloway

Gastric neuroendocrine neoplasms are rare, and limited evidence links B7 family ligands and receptors to their clinical relevance. This study assessed immune checkpoint markers in 112 gastric neuroendocrine neoplasm samples by immunohistochemistry, quantifying PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155. High expression levels were frequent and associated with multiple clinicopathological features, while survival analyses identified prognostic relationships. Multivariate models indicated CD155 and additional factors as independent predictors of overall survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Gastric neuroendocrine neoplasms and clinical subtypes

WHO histological grading and prognosis

Management approaches and immunotherapy context

Methods

Immunohistochemistry cohort and marker panel

Associations with clinicopathological variables and survival

Results

Expression rates of PD-L1/PD-L2 and B7 family ligands

Survival associations from Kaplan-Meier and Cox models

Discussion

Interpretation of checkpoint expression and clinical indicator potential

ARTICLE 1 | INTRODUCTION: 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.
METHODS: 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. | | --- | | | | | | | | | Expression Patterns of Immune Checkpoint Molecules and Their Clinical Values in Gastric Neuroendocrine Neoplasms Mengjie Liang, PhD1 , *, Junren Lu, MD1 , *, Xingzhou Wang, PhD1 , *, Peng Song, PhD 1 , *, Shichao Ai, PhD1 , *, Daming Cai, PhD1 , Feng Sun, PhD1, Xiaofeng Lu, PhD1, Meng Wang, PhD1, Shuang Fu, BM2, Heng Yu, MD1, Wenxian Guan, PhD1 and Xiaofei Shen, PhD1 ,3 STOMACH 1Department of General Surgery, Division of Gastric Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; 2Department of Anesthesiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; 3Department of General Surgery, Division of Gastric Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China. Correspondence: Xiaofei Shen. E-mail: [dg1535058@smail.nju.edu.cn](dg1535058@smail.nju.edu.cn); Heng Yu, PhD. E-mail: [yuhmed@163.com](yuhmed@163.com); Wenxian Guan. E-mail: 15850502391@ [163.com](163.com); Shuang Fu. E-mail: [13764038@qq.com](13764038@qq.com). *Mengjie Liang, Junren Lu, Xingzhou Wang, Peng Song, and Shichao Ai contributed equally as co-first author. Received October 10, 2024; accepted March 27, 2025; published online April 4, 2025 © 2025 The Author(s) . Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology American College of Gastroenterology Clinical and Translational Gastroenterology STOMACH RESULTS: 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 5 0.0002, P 5 0.0319 and P 5 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 5 0.007, P 5 0.030, and P 5 0.019, respectively) . DISCUSSION: We detected variable expression of the PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins ing-NENs. These results suggest that the expression level of CD155 may be a vital indicator of OS inpatients with g-NENs. B7 family ligands/receptors could be potential immunotherapeutic targets for g-NENs. KEYWORDS: B7 family receptors/ligands; gastric neuroendocrine neoplasms; overall survival; immunotherapy Clinical and Translational Gastroenterology 2025;16:e00842. [https://doi.org/10.14309/ctg.0000000000000842](https://doi.org/10.14309/ctg.0000000000000842) INTRODUCTION Gastroenteropancreatic neuroendocrine tumors (NETs), which include gastric neuroendocrine neoplasms (g-NENs), are increasingly common(1) . G-NENS are neoplasms derived from the enterochromaﬃn-like cells of the gastric mucosa. These tumors are rare lesions with indolent behavior and neuroendocrine differentiation. Gastric NETs are relatively rare lesions

FAQs

Which immune checkpoint molecules were evaluated in gastric neuroendocrine neoplasms?

The study quantified PD-L1, PD-L2, B7-H3, B7-H4, LGALS9 (galectin-9), and CD155 in 112 g-NEN samples using immunohistochemistry.

How were the marker levels related to clinicopathological features?

Elevated expression of the studied markers was significantly associated with several clinicopathological characteristics across the cohort.

Which factors were independent predictors of overall survival?

Multivariate Cox regression indicated high CD155 expression, vasculature invasion, and worse World Health Organization pathological grade as independent prognostic factors for overall survival.

Sep 23, 2026

Uploaded by Quinn Holloway