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喉发育不良的转录组分析。

A Transcriptomic Analysis of Laryngeal Dysplasia.

机构信息

Department of Surgical Pathology, European Institute of Oncology IRCCS, 20141 Milan, Italy.

Division of Otolaryngology Head and Neck Surgery, European Institute of Oncology IRCCS, 20141 Milan, Italy.

出版信息

Int J Mol Sci. 2024 Sep 7;25(17):9685. doi: 10.3390/ijms25179685.

Abstract

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.

摘要

本文描述了先天免疫系统的转录改变如何将发育异常分为侵袭性形式,尽管进行了治疗,但很快且更容易复发,以及其他进展缓慢且更易于治疗的形式。它详细说明了免疫系统如何改变细胞外基质,促进肿瘤进展,以及感染如何通过增加上皮损伤(由于表面免疫球蛋白的丧失)和放大炎症反应来增强疾病进展。我们研究了这些失调基因是否与疾病进展、延迟或恢复有关。这些转录改变是使用基于 RNA 的下一代测序 (NGS) 面板 Oncomine Immune Response Research Assay (OIRRA) 观察到的,该面板用于测量与淋巴细胞调节、细胞因子信号传导、淋巴细胞标志物和检查点途径相关的基因表达。在分析过程中,显然某些改变将发育异常分为两类:进展性或非进展性。将来,这些生物学改变是提供新的治疗方式的第一步,这些新的治疗方式包括当前全身性或局部应用的不同类别的药物,包括顺铂和氟尿嘧啶等经典化疗药物、已有的药物如芬维 A 酯以及新的检查点抑制剂药物如纳武单抗和派姆单抗,以及更新的选择如 T 细胞疗法(CAR-T)。根据这些观察到的改变,可以区分哪些发育异常会进展或不会进展,或者是否会很快复发。这些信息将来可能成为确定密切随访、尽量减少手术干预、为每个患者制定正确和个性化治疗方案以及在进行特定临床试验后调整新药物治疗的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eda/11395940/600dac2d5ee0/ijms-25-09685-g001.jpg

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