Evidence map›Paper›PMID 39552563›Full record

ArticleThe oncologist2025

Overestimation of clinical N-staging in microsatellite instable gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics.

Chun-Yi Tsai, Tzong-Shyuan Tai, Shih-Chiang Huang, Tsung-Hsing Chen, Jun-Te Hsu, Chun-Nan Yeh, Ying-Chieh Lai, Gigin Lin, Ta-Sen Yeh

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Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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9 authors.

Chun-Yi TsaiDepartment of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Tzong-Shyuan TaiDepartment of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Shih-Chiang HuangDepartment of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Tsung-Hsing ChenDepartment of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Jun-Te HsuDepartment of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Chun-Nan YehDepartment of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Ying-Chieh LaiDepartment of Radiology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Gigin LinDepartment of Radiology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Ta-Sen YehDepartment of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.ORCID 0000-0002-1830-9466

Funding

Chang Gung Medical Research Program, Taiwan CMRPG5N0061
6 · The paper itself

Abstract

backgroundMicrosatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation. MATERIALS AND

methodsWe conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors.

resultsMultivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts.

conclusionFrequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options.

Indexed as

CD8-Positive T-LymphocytesMicrosatellite InstabilityStomach NeoplasmsVascular Endothelial Growth Factor CAdultAgedFemaleHumansLymphatic MetastasisMaleMiddle AgedNeoplasm StagingPrognosisSignal TransductionVascular Endothelial Growth Factor Receptor-3Vascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3VEGFC protein, humanCD8+ T cellclinical N-staginglymph node ratiomicrosatellite instable gastric cancerVEGF-C

Identifiers

PMID39552563
PMCPMC12311297

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