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Expression Patterns of Immune Checkpoint Molecules and Their Clinical Values in Gastric Neuroendocrine Neoplasms
Mengjie Liang1, Junren Lu1, Xingzhou Wang1
1Department of General Surgery, Division of Gastric Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University , Nanjing, China.
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.
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 = 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).
Discussion:
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.
Insights
This study investigated B7 family ligands in gastric neuroendocrine neoplasms (g-NENs). High CD155 expression is linked to poorer survival, suggesting it as a prognostic indicator and potential immunotherapy target for g-NENs.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Gastric neuroendocrine neoplasms (g-NENs) are rare stomach tumors.
- Limited data exist on B7 family ligands/receptors in g-NENs.
- This study addresses this knowledge gap in 112 g-NEN patients.
Purpose of the Study:
- To map and quantify the expression of B7 family ligands/receptors in g-NENs.
- To evaluate the clinical significance of these markers in relation to clinicopathological variables and patient survival.
Main Methods:
- Immunohistochemistry was used to analyze 112 g-NEN samples.
- Expression levels of programmed cell death ligand 1 and 2 (PD-L1, PD-L2), B7-H3, B7-H4, recombinant human galectin-9 (LGALS9), and CD155 were quantified.
- Associations with clinicopathological variables and survival were assessed using Kaplan-Meier analysis and Cox regression.
Main Results:
- High expression rates were observed for PD-L1 (37.5%), PD-L2 (55.4%), B7-H3 (46.4%), B7-H4 (37.5%), LGALS9 (46.4%), and CD155 (51.8%).
- Elevated expression of these markers correlated significantly with various clinicopathological characteristics.
- High CD155, B7-H3, PD-L2, and LGALS9 expression were associated with poorer overall survival (OS).
- Multivariate analysis identified high CD155 expression, vasculature invasion, and higher WHO grade as independent prognostic factors for OS.
Conclusions:
- Variable expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins was detected in g-NENs.
- CD155 expression level may serve as a critical indicator of overall survival in g-NEN patients.
- B7 family ligands/receptors represent potential targets for immunotherapy in g-NEN treatment.
