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HIGD1B 作为一种新型预后生物标志物,参与调节肿瘤微环境和免疫细胞浸润;其过表达导致胃癌患者预后不良

英文原题:HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.

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HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.

PubMed 2024/07/23(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

本研究探讨了 HIGD1B 在 GC 中的潜在机制及诊断和预后价值,并将 HIGD1B 确定为 GC 的有价值生物标志物和可能的治疗靶点。

研究思路结论见上方概要

HIGD1B(HIG1缺氧诱导域家族成员1B)是一个与多种疾病发生和发展相关的蛋白编码基因。然而,其在胃癌(GC)中的确切功能仍不清楚。

通过TCGA和GEO数据库确定HIGD1B的表达,并通过实验进行验证。通过Kaplan-Meier(K-M)曲线分析HIGD1B与GC患者预后之间的关联。随后,研究人员利用ROC曲线评估HIGD1B的诊断能力,并采用COX分析探究GC的风险因素。然后对差异表达基因(DEGs)进行功能富集分析,并生成列线图以预测GC患者的生存结局和概率。此外,我们评估了HIGD1B与免疫细胞浸润之间的相互作用,并预测了GC患者对治疗的敏感性。

HIGD1B在GC组织和细胞系中显著升高,HIGD1B高表达的患者预后较差。此外,HIGD1B与不同的分级、分期和T分期相关。HIGD1B的生存ROC曲线和五年列线图分别为0.741和0.735,提示具有适当的诊断效能。根据Cox回归分析,HIGD1B是胃癌预后的独立危险因素(p<0.01)。GSEA分析表明,HIGD1B与癌症形成和晚期通路密切相关。此外,HIGD1B高表达的患者表现出更高水平的肿瘤浸润免疫细胞(TIICs),并且在化疗和免疫治疗后更可能发生免疫逃逸和耐药。

展开英文摘要原文

HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear.

The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy.

HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy.

This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC.

论文信息

作者
Wang S、Zhang S、Li X、Li X、Zhao S、Guo J、Wang S、Wang R
单位
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39108265 · DOI 10.3389/fimmu.2024.1415148