Investigating the Impact of B Cell-Related Genes on Colorectal Cancer Immunosuppressive Environment and Immunotherapy Evasion

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2025-01-27 DOI:10.1002/ddr.70053

Haixia Wu, Yilin Yu, Zhiping Wang, Shiji Wu, Lingdong Shao, Liang Hong, Jianjian Qiu, Xueqing Zhang, Junxin Wu

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Abstract

We aimed to elucidate the prognostic and immunological roles of B cell-related genes in colorectal cancer (CRC). This study comprehensively integrated data from single-cell RNA-sequencing, TCGA, GEO, IMvigor210, GDSC, CancerSEA, HPA, and TISIDB databases to explore prognostic implications and immunological significance of B cell-related gene signature in CRC. We identified seven prognostically significant B cell-related genes for constructing a risk score. Clinical relevance analysis indicated that this risk score served as an independent prognostic factor, with the model accurately predicting patient outcomes. GSEA results implicated the risk score in immune function, cell cycle, and DNA replication. Immune infiltration analysis revealing lower levels of B cells, CD4+ cells, and CD8+ cells in the high-risk group, correlating with decreased immune activity and function. IMvigor210 and TIDE analysis indicated poorer prognosis among high-risk group patients receiving immune therapy. Additionally, the high-risk group exhibited lower sensitivity to immune therapy. Further analysis of drug sensitivity suggested higher resistance to common chemotherapy drugs among high-risk groups. Finally, we identified HSPA1A as the gene with the strongest association with immune and inflammatory responses. Validation of HSPA1A protein expression and prognosis demonstrated elevated expression in CRC compared to normal colorectal tissue, further reinforcing its association with poorer prognosis and higher tumor stage. The risk score exhibited substantial variations in clinical characteristics, functional mechanism, TMB, drug sensitivity, immune cell infiltration, and immune subtype. Our findings may aid in clinical decision-making by shedding light on novel and promising biomarkers for CRC prognosis and immunotherapy response prediction.

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B细胞相关基因对结直肠癌免疫抑制环境及免疫治疗逃避的影响

我们旨在阐明B细胞相关基因在结直肠癌（CRC）中的预后和免疫学作用。本研究综合了来自单细胞rna测序、TCGA、GEO、IMvigor210、GDSC、CancerSEA、HPA和TISIDB数据库的数据，探讨了B细胞相关基因标记在结直肠癌中的预后意义和免疫学意义。我们确定了七个具有预后意义的B细胞相关基因，用于构建风险评分。临床相关性分析表明，该风险评分可作为独立的预后因素，该模型可准确预测患者预后。GSEA结果涉及免疫功能、细胞周期和DNA复制的风险评分。免疫浸润分析显示，高危组B细胞、CD4+细胞和CD8+细胞水平较低，与免疫活性和功能下降有关。IMvigor210和TIDE分析提示高危组患者接受免疫治疗预后较差。此外，高危组对免疫治疗的敏感性较低。进一步的药物敏感性分析表明，高危人群对常见化疗药物的耐药性较高。最后，我们确定了HSPA1A是与免疫和炎症反应最强相关的基因。HSPA1A蛋白表达和预后的验证表明，与正常结直肠组织相比，结直肠癌中HSPA1A蛋白表达升高，进一步强化了其与较差预后和较高肿瘤分期的相关性。风险评分在临床特征、功能机制、TMB、药物敏感性、免疫细胞浸润、免疫亚型等方面存在较大差异。我们的研究结果可能有助于临床决策，揭示新的和有前途的生物标志物，用于CRC预后和免疫治疗反应预测。

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来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.