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在头颈部鳞状细胞癌中,神经纤毛蛋白1(NRP1)的过表达通过加速免疫抑制与不良预后相关。

Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma.

作者信息

Yang Xueming, Xu Teng, Song Xiaomeng, Wu Yunong

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

出版信息

Int J Gen Med. 2023 Jul 4;16:2819-2829. doi: 10.2147/IJGM.S409336. eCollection 2023.

DOI:10.2147/IJGM.S409336
PMID:37426519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10329464/
Abstract

BACKGROUND

Neuropilin-1 (NRP1) is a significant molecular structure that participates in many diseases progress including malignant tumors. However, its role in head and neck squamous cell carcinoma (HNSCC) remains to be uncovered. In this study, we determined the function of NRP1 as a crucial biomarker in proliferation, metastasis and immunosuppression in HNSCC.

METHODS

We collected samples of normal tissues (n = 18) and HNSCC tissues (n = 202) for immunohistochemical staining of NRP1 and evaluated its correlation to clinical prognostic characteristics. Furthermore, we enrolled 37 HNSCC patients received immune checkpoint blockade (ICB) treatment with defined therapeutic effects records. The biological process, signal pathways, and immune infiltration relevance to NRP1 were analyzed utilized transcriptome data from The Cancer Genome Atlas (TCGA).

RESULTS

The NRP1 protein expression was significantly upregulated in HNSCC tissue and was associated with T stage, N stage, histological differentiation, recurrence and NRP1 expression. The high expression of NRP1 indicated poor survival rate and was found to be an independent prognosis factor. Enrichment analysis showed that NRP1 was associated with cell adhesion, extracellular matrix organization, homophilic cell adhesion via plasma membrane in biological process and neuroactive ligand-receptor interaction, protein digestion and absorption, calcium signal pathways. Moreover, NRP1 mRNA level was found positively correlated to cancer associated fibroblast cells, Treg cells and macrophage/monocyte cells.

CONCLUSION

NRP1 might be likely to develop into a potential immunoregulation target as well as a predictive biomarker in HNSCC immune treatment.

摘要

背景

神经纤毛蛋白-1(NRP1)是一种重要的分子结构,参与包括恶性肿瘤在内的多种疾病进展。然而,其在头颈部鳞状细胞癌(HNSCC)中的作用仍有待揭示。在本研究中,我们确定了NRP1作为HNSCC增殖、转移和免疫抑制中关键生物标志物的功能。

方法

我们收集了正常组织样本(n = 18)和HNSCC组织样本(n = 202)用于NRP1的免疫组织化学染色,并评估其与临床预后特征的相关性。此外,我们招募了37例接受免疫检查点阻断(ICB)治疗且有明确治疗效果记录的HNSCC患者。利用来自癌症基因组图谱(TCGA)的转录组数据,分析了与NRP1相关的生物学过程、信号通路和免疫浸润情况。

结果

NRP1蛋白表达在HNSCC组织中显著上调,且与T分期、N分期、组织学分化、复发及NRP1表达相关。NRP1高表达提示生存率低,且被发现是一个独立的预后因素。富集分析表明,NRP1在生物学过程中与细胞黏附、细胞外基质组织、通过质膜的同种型细胞黏附以及神经活性配体-受体相互作用、蛋白质消化和吸收、钙信号通路相关。此外,发现NRP1 mRNA水平与癌症相关成纤维细胞、调节性T细胞和巨噬细胞/单核细胞呈正相关。

结论

NRP1可能会发展成为HNSCC免疫治疗中潜在的免疫调节靶点以及预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/78c9c6bae758/IJGM-16-2819-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/42a5af20e23f/IJGM-16-2819-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/46b29ce0c10d/IJGM-16-2819-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/95c7257fcf49/IJGM-16-2819-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/64342ffb08dd/IJGM-16-2819-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/78c9c6bae758/IJGM-16-2819-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/42a5af20e23f/IJGM-16-2819-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/46b29ce0c10d/IJGM-16-2819-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/95c7257fcf49/IJGM-16-2819-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/64342ffb08dd/IJGM-16-2819-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67e/10329464/78c9c6bae758/IJGM-16-2819-g0005.jpg

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A high CD8 to FOXP3 ratio in the tumor stroma and expression of PTEN in tumor cells are associated with improved survival in non-metastatic triple-negative breast carcinoma.
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