Zhang Chengjuan, Wang Tingjie, Yuan Jing, Wang Tao, Ma Bin, Xu Benling, Bai Ruihua, Tang Xiance, Zhang Xiaojie, Wu Minqing, Lei Tianqi, Xu Wenhao, Guo Yongjun, Li Ning
Center of Bio-Repository, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Henan Key Laboratory of Molecular Pathology, Zhengzhou, Henan, P. R. China.
BMC Cancer. 2025 Apr 12;25(1):674. doi: 10.1186/s12885-025-14046-7.
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.
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.
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.
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.
免疫新辅助治疗因其在癌症治疗方面的显著进展而备受关注。本研究旨在通过对一项注册临床试验队列的样本进行全面的多组学分析，探讨免疫新辅助治疗的分子机制。
从16例患者中收集术前样本，其中12例获取了术后样本。采用RNA测序（RNA-seq）和Olink蛋白质组学技术来鉴定新辅助治疗前后的关键基因。使用加权基因共表达网络分析（WGCNA）构建加权共表达网络。此外，基于RNA-seq的标准化表达数据，使用xCell计算浸润免疫细胞的比例。
根据新辅助免疫治疗的肿瘤退缩分级（TRG），将患者分为T1组（疗效良好）和T2组（疗效较差）。与T2组（TRG2和TRG3）相比，T1组（TRG0和TRG1）在与炎症反应和髓系白细胞活化相关的通路中存在显著差异。此外，T1组的CD8 T细胞和B细胞水平升高。在受试者工作特征（ROC）曲线下面积最大的前两个因素是CD8a分子（CD8A）（1.000）和C-C基序趋化因子配体20（CCL20）（0.967）。此外，与T2组相比，T1组中胎盘生长因子（PGF）和TNF受体超家族成员21（TNFRSF21）蛋白的表达显著增加。CD8A的高表达和PGF的高表达分别与胃癌患者的良好预后和不良预后相关。免疫浸润分析显示CD8A与树突状细胞（DC）水平呈正相关，而与髓系来源的抑制细胞（MDSC）水平呈负相关。
通过多组学分析，我们发现CD8A与增强的治疗反应和肿瘤退缩相关。相比之下，PGF似乎对治疗结果产生不利影响，这表明影响胃癌免疫新辅助治疗疗效的因素之间存在复杂的相互作用。
