Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy

Chengjuan Zhang; Tingjie Wang; Jing Yuan; Tao Wang; Bin Ma; Benling Xu; Ruihua Bai; Xiance Tang; Xiaojie Zhang; Minqing Wu; Tianqi Lei; Wenhao Xu; Yongjun Guo; Ning Li

doi:10.1186/s12885-025-14046-7

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Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy

Journal article

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Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy

Chengjuan Zhang, Tingjie Wang, Jing Yuan, Tao Wang, Bin Ma, Benling Xu, Ruihua Bai, Xiance Tang, Xiaojie Zhang, Minqing Wu, …

BMC cancer, Vol.25(1), 674

2025

DOI: https://doi.org/10.1186/s12885-025-14046-7

PMID: 40221689

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Abstract

Adult

Aged

Biomarkers, Tumor - genetics

Biomarkers, Tumor - metabolism

CD8 Antigens - genetics

CD8 Antigens - metabolism

CD8-Positive T-Lymphocytes - immunology

Female

Gene Expression Regulation, Neoplastic

Humans

Immunotherapy - methods

Male

Middle Aged

Neoadjuvant Therapy - methods

Prognosis

Stomach Neoplasms - genetics

Stomach Neoplasms - immunology

Stomach Neoplasms - metabolism

Stomach Neoplasms - mortality

Stomach Neoplasms - pathology

Stomach Neoplasms - therapy

Background Immunoneoadjuvant therapy has gained significant attention due to its remarkable advancements in cancer treatment. This study aimed to investigate the molecular mechanisms underlying immunoneoadjuvant therapy through a comprehensive multiomics analysis of samples from a registered clinical trial cohort. Methods Preoperative samples were collected from 16 patients, and postoperative samples were obtained from 12 among them. RNA sequencing (RNA-seq) and Olink proteomics were employed to identify key genes before and after neoadjuvant treatment. The weighted coexpression network was constructed using Weighted gene co-expression network analysis (WGCNA). Furthermore, the proportion of infiltrated immune cells was calculated using xCell based on normalized expression data derived from RNA-seq. Results Patients were stratified into T1 (good efficacy) and T2 (poor efficacy) groups based on Tumor Regression Grade (TRG) to neoadjuvant immunotherapy. Compared to the T2 group (TRG2 and TRG3), the T1 group (TRG0 and TRG1) showed significant differences in pathways related to inflammatory response and myeloid leukocyte activation. Furthermore, the T1 group exhibited elevated levels of CD8+ T cells and B cells. The top two factors with the highest area under the Receiver Operating Characteristic (ROC) curve were CD8a molecule (CD8A) (1.000) and C-C motif chemokine ligand 20 (CCL20) (0.967). Additionally, the expression of placenta growth factor (PGF) and TNF receptor superfamily member 21 (TNFRSF21) proteins significantly increased in the T1 group compared to the T2 group. High expression of CD8A and PGF were associated with favorable and poor prognosis in gastric cancer patients, respectively. Immunoinfiltration analysis revealed a positive correlation between CD8A and dendritic cell (DC) levels, while a negative correlation was observed with myeloid-derived suppressor cell (MDSC) levels. Conclusions Through multiomics analysis, we discovered that CD8A is linked to enhanced treatment response and tumor regression. In contrast, PGF appears to exert adverse effects on treatment outcomes, suggesting a complex interplay of factors influencing the efficacy of immunoneoadjuvant therapy in gastric cancer.

Details

Title: Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy
Authors/Creators: Chengjuan Zhang - Henan Cancer Hospital
Tingjie Wang - Henan Cancer Hospital
Jing Yuan - Henan Cancer Hospital
Tao Wang - The Kids Research Institute Australia, School of Medicine, the University of Western Australia, Nedlands, WA, Australia
Bin Ma - Murdoch University
Benling Xu - Zhengzhou University
Ruihua Bai - Henan Cancer Hospital
Xiance Tang - Henan Cancer Hospital
Xiaojie Zhang - Zhengzhou University
Minqing Wu - Henan Cancer Hospital
Tianqi Lei - Zhengzhou University
Wenhao Xu - Henan Cancer Hospital
Yongjun Guo - Zhengzhou University
Ning Li - Zhengzhou University
Publication Details: BMC cancer, Vol.25(1), 674
Publisher: BioMed Central Ltd unless otherwise stated. Part of Springer Nature.
Number of pages: 13
Grant note: 242300420095 / Natural Science Foundation of Henan Province Project 201300310400 / Major public welfare projects in Henan Province- Research and development of new technologies for tumor liquid biopsy and immunotherapy YXKC2021032, YXKC2021008 / The Health Science and Technology Innovation Project for Young people of Henan Provincial SBGJ202302028 / Henan Province and Ministry of Health of Medical Science and Technology JC23858081 / Zhengzhou University young teachers basic research training project
Identifiers: 991005762551807891
Murdoch Affiliation: School of Medical, Molecular and Forensic Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.214 Checkpoint Inhibition
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine