透明细胞肾细胞癌中KIM-1 （HAVCR1）表达与肿瘤免疫微环境的关系

IF 3.3 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2025-07-28 DOI:10.2174/0115665232402424250721114133

Panagiotis J Vlachostergios, Athanasios Karathanasis, Foteini Karasavvidou, Vassilios Tzortzis

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It is also expressed in renal cell carcinoma (RCC).Objective: This study examined the immune landscape of clear cell RCC in association with HAVCR1 expression.Methods: Next-generation sequencing (NGS) data from ccRCC tumor samples of patients from The Cancer Genome Atlas (TCGA) were interrogated for enrichment of immune infiltrates and checkpoints in tumors harboring high HAVCR1 mRNA expression or/and amplification.Results: HAVCR1 mRNA expression was positively associated with presence of CD8 (r = 0.254, p = 3.03 x 10-8) and CD4 T-cells (r = 0.329, p = 3.98 x 10-13), while it was negatively associated with T-regulatory (T-regs) (r = ̶ 0.2, p = 1.47 x 10-5) and myeloid-derived suppressor cells (MDSCs) (r = ̶.0.285, p = 4.92 x 10-10). 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引用次数: 0

摘要

肾损伤分子1 （KIM-1）是一种表达于近端小管的细胞表面糖蛋白，由甲型肝炎病毒细胞受体1 （HAVCR1）基因编码。它也在肾细胞癌（RCC）中表达。目的：本研究探讨透明细胞RCC的免疫景观与HAVCR1表达的关系。方法：对来自癌症基因组图谱（TCGA）的患者ccRCC肿瘤样本的下一代测序（NGS）数据进行查询，以富集具有高HAVCR1 mRNA表达或/和扩增的肿瘤中的免疫浸润和检查点。结果：HAVCR1 mRNA表达与CD8 （r = 0.254, p = 3.03 × 10-8）和CD4 t细胞（r = 0.329, p = 3.98 × 10-13）呈正相关，与t -调节性细胞（T-regs）（r = 0.2, p = 1.47 × 10-5）和髓源性抑制细胞（MDSCs）（r = 0.285, p = 4.92 × 10-10）呈负相关。HAVCR1基因的表达与免疫检查点PD-L1 (CD274) （r = 0.331, p = 4.64 × 10-15）和CTLA4 mRNA表达（r = 0.085, p = 0.05）呈正相关。HAVCR1转录物水平与多态性1 （PBRM1）表达水平呈正相关（r = 0.276, p = 9.36 × 10-11），与brca相关蛋白1 （BAP1）基因表达水平呈负相关（r = 0.134, p = 1.94 × 10-3）。讨论：该研究表明，透明细胞RCC中HAVCR1 （KIM-1）的高表达与以CD8/CD4 t细胞浸润和免疫检查点表达增加为特征的独特免疫特征相关，提示在预测免疫治疗反应中具有潜在作用，尽管观察性和对TCGA数据的依赖限制了因果推断。结论：总的来说，KIM-1在透明细胞RCC中有潜在的免疫调节作用。这可以用于预测辅助免疫治疗的获益。

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Association of KIM-1 (HAVCR1) Expression with the Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.

Introduction: Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed in the proximal tubules and encoded by the hepatitis A virus cellular receptor 1 (HAVCR1) gene. It is also expressed in renal cell carcinoma (RCC).

Objective: This study examined the immune landscape of clear cell RCC in association with HAVCR1 expression.

Methods: Next-generation sequencing (NGS) data from ccRCC tumor samples of patients from The Cancer Genome Atlas (TCGA) were interrogated for enrichment of immune infiltrates and checkpoints in tumors harboring high HAVCR1 mRNA expression or/and amplification.

Results: HAVCR1 mRNA expression was positively associated with presence of CD8 (r = 0.254, p = 3.03 x 10-8) and CD4 T-cells (r = 0.329, p = 3.98 x 10-13), while it was negatively associated with T-regulatory (T-regs) (r = ̶ 0.2, p = 1.47 x 10-5) and myeloid-derived suppressor cells (MDSCs) (r = ̶.0.285, p = 4.92 x 10-10). HAVCR1 amplification was also associated with CD8 (p = 0.0019), CD4 T cells (p = 0.0002) while expression of HAVCR1 gene was positively associated with immune checkpoints PD-L1 (CD274) (r = 0.331, p = 4.64 x 10-15) and CTLA4 mRNA expression (r = 0.085, p = 0.05). HAVCR1 transcript levels were directly correlated with those of Polybromo-1 (PBRM1) (r = 0.276, p = 9.36 x 10-11) while inversely related with BRCA-associated protein 1 (BAP1) gene expression (r = ̶ 0.134, p = 1.94 x 10-3).

Discussion: The study reveals that high HAVCR1 (KIM-1) expression in clear cell RCC is associated with a distinct immune profile characterized by increased CD8/CD4 T-cell infiltration and immune checkpoint expression, suggesting a potential role in predicting immunotherapy response, though the observational nature and reliance on TCGA data limit causal inference.

Conclusions: Collectively, a potential immune-regulatory role of KIM-1 in clear cell RCC is implicated. This could be exploited for predicting benefit from adjuvant immunotherapy.

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.