Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, Sydney, NSW, Australia; Central Clinical School, Faculty of Medicine and Health, the University of Sydney, Sydney, NSW, Australia; Faculty of Medicine, University of New South Wales, Randwick, Sydney, NSW, Australia.
Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, Sydney, NSW, Australia.
Surg Oncol. 2022 Jun;42:101770. doi: 10.1016/j.suronc.2022.101770. Epub 2022 Apr 14.
Perinueral invasion (PNI) is recognized as an independent adverse prognostic factor associated with shorter disease free and disease specific survival in a range of malignancies. However, not all histologically detected PNI demonstrate aggressive biologic behaviour. Herein, we systematically review the literature to identify neurotrophic biomarkers that may potentially be used to predict the biologic potential of PNI.
A systematic review was conducted based on PRISMA guidelines utilising the search terms 'PNI', 'DNA' and 'RNA' analysis in select malignancies following registry of the search strategy on PROSPERO. The biologic role of the molecular markers identified through the literature review was examined using publicly available databases, such as Gene Cards and Kyoto Encyclopedia of Genes and Genomes (KEGG) with a focused literature review of the identified pathways.
The systematic search identified 256 studies, of which 78 studies were suitable for data extraction. A variety of methodologies including immunohistochemistry, immunoblotting, nucleic acid sequencing, Luciferase assays and CRISPR techniques have been undertaken to evaluate the biologic potential of PNI. The studies evaluated 136 unique molecules. Of these, only 15 molecules were investigated through multiple studies with concordant results or had robust functional analyses. Three pathways were identified as playing a role in PNI, namely; the epithelial-mesenchymal transition pathway, neurotrophic pathway and Notch pathway.
Our understanding of the complex and reciprocal interaction between tumour and nerve cells that drives PNI is still evolving. The knowledge gaps can largely be attributed to publication bias, lack of availability of high-quality patient derived tissues and limitations of currently available technology. This review summarises the current knowledge regarding development and progression of PNI that can be harnessed for prognostication and treatment. This review also summarises the lacunae in our understanding of the pathogenesis of PNI thus identifying avenues for future studies.
围神经浸润（PNI）被认为是一种独立的不良预后因素，与多种恶性肿瘤的无病生存期和疾病特异性生存期缩短相关。然而，并非所有组织学检测到的 PNI 都表现出侵袭性的生物学行为。在此，我们系统地回顾了文献，以确定可能用于预测 PNI 生物学潜力的神经营养生物标志物。
根据 PRISMA 指南进行系统评价，使用在 PROSPERO 上注册的搜索策略，在选定的恶性肿瘤中使用“PNI”、“DNA”和“RNA”分析的搜索词。通过文献综述，使用基因卡片和京都基因与基因组百科全书（KEGG）等公共数据库来检查通过文献综述确定的分子标记的生物学作用，并对确定的途径进行了重点文献综述。
系统搜索确定了 256 项研究，其中 78 项研究适合提取数据。已经采用了各种方法，包括免疫组织化学、免疫印迹、核酸测序、荧光素酶测定和 CRISPR 技术，以评估 PNI 的生物学潜力。这些研究评估了 136 个独特的分子。其中，只有 15 个分子通过具有一致结果或具有强大功能分析的多项研究进行了研究。确定了三个通路在 PNI 中发挥作用，即上皮-间充质转化通路、神经营养通路和 Notch 通路。
我们对肿瘤细胞和神经细胞之间相互作用的复杂和相互作用的理解仍在不断发展。知识空白很大程度上归因于发表偏倚、缺乏高质量的患者来源组织和现有技术的局限性。本综述总结了目前关于 PNI 发生和进展的知识，这些知识可用于预后和治疗。本综述还总结了我们对 PNI 发病机制理解的空白，从而确定了未来研究的途径。
