PCDHB家族在胃癌中的综合评价：预后意义、免疫浸润及PCDHB5致癌作用的实验验证

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-08-05 DOI:10.1016/j.intimp.2025.115318

Juanjuan Zhou , Jinbo Zhan , Hongjiao Zhang , Liping Liu , Yan He , Yi Le , Weiqi Liu , Ling Zhou , Xiaojun Xiang

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引用次数: 0

摘要

原钙粘蛋白B家族基因（PCDHBs）在肿瘤进展中发挥重要作用，但其在胃癌中的具体功能尚不清楚。本研究旨在研究pcdhb在胃癌中的表达规律，探讨其对免疫浸润及患者预后的影响，并通过体外实验初步验证PCDHB5的功能作用及其机制。利用TCGA数据库的多组学数据，我们发现大多数pcdhb在胃癌中显著上调，错义突变是最常见的突变类型。此外，我们发现PCDHBs与ESTIMATE评分和TIDE评分呈正相关，与微卫星不稳定性和肿瘤突变负担负相关，表明它们参与形成免疫抑制的肿瘤微环境和对免疫治疗的不良反应。值得注意的是，通过LASSO回归和多因素分析，PCDHB5被确定为与胃癌总生存期（OS）和无进展生存期（PFS）相关的关键基因。基于这些发现，我们构建了结合PCDHB5表达的nomogram来预测胃癌患者的预后。功能分析和分子生物学技术证实PCDHB5在胃癌中高表达，可能通过调控Wnt/β-catenin信号通路促进胃癌细胞增殖、迁移和侵袭。综上所述，本研究全面分析了PCDHBs在胃癌中的作用，揭示了其在肿瘤免疫和预后中的作用，并强调了PCDHB5在胃癌进展中的功能作用及其作为治疗靶点的潜力。

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Comprehensive evaluation of the PCDHB family in gastric cancer: Prognostic significance, immune infiltration, and experimental validation of PCDHB5's oncogenic role

The protocadherin B family genes (PCDHBs) play a significant role in tumor progression, yet their specific functions in gastric cancer remain insufficiently understood. This study aims to investigate the expression patterns of PCDHBs in gastric cancer, explore their influence on immune infiltration and patient prognosis, and preliminarily validate the functional role and underlying mechanisms of PCDHB5 through in vitro experiments. Using multi-omics data from the TCGA database, we found that most PCDHBs are significantly upregulated in gastric cancer, with missense mutations being the most common mutation type. Furthermore, we found the positive correlation between PCDHBs and the ESTIMATE score, as well as the TIDE score, and the negative correlation with microsatellite instability and tumor mutational burden, suggesting their involvement in shaping an immunosuppressive tumor microenvironment and poor response to immunotherapy. Notably, through LASSO regression and multivariate analysis, PCDHB5 was identified as a key gene correlated with overall survival (OS) and progression-free survival (PFS) in gastric cancer. Based on these findings, we constructed a nomogram incorporating PCDHB5 expression to predict the prognosis of gastric cancer patients. Functional assays and molecular biology techniques confirmed that PCDHB5 is highly expressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion, potentially through the regulation of the Wnt/β-catenin signaling pathway. In conclusion, this study provides a comprehensive analysis of PCDHBs in gastric cancer, revealing their roles in tumor immunity and prognosis, and highlights the functional role of PCDHB5 in gastric cancer progression and its potential as a therapeutic target.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.