Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.

Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.
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DOI:
10.1371/journal.pone.0258187
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Panahiazar M
Panahiazar M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Allen DZ;Aljabban J;Silverman D;McDermott S;Wanner RA;Rohr M;Hadley D;Panahiazar M

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鼻咽癌(NPC)是一种上皮来源的癌症,在某些人群中具有高发病率。虽然鼻咽癌伴随放化疗的缓解率很高,但复发率很高,治疗的下游发病率很高。因此,寻找替代疗法势在必行。我们采用了搜索标签分析资源(STARGEO)平台,使用国家生物技术中心(NCBI)的基因表达综合数据库(GEO)进行荟萃分析,以定义NPC发病机制。我们从NPC公共患者数据中鉴定了111个肿瘤样本和43个健康鼻咽上皮样本。我们在致病途径分析(IPA)中分析了相关的特征,限制了疾病和对照样品之间显示统计学显著性(p<0.05)和绝对实验对数比大于0.15的基因。我们的荟萃分析确定了NPC组织中脂多糖(LPS)诱导的组织损伤的激活。此外,白细胞介素-1(IL-1)和SB 203580是最高的上游调节因子。肿瘤发生相关基因如同源框A10(HOXA 10)和胰高血糖素-内过氧化物合酶2(PTGS 2或考克斯-2)以及与细胞外基质降解相关的基因如基质金属蛋白酶1和3(MMP-1、MMP-3)也上调。记录了编码与维持健康的鼻呼吸上皮结构完整性相关的蛋白质的基因表达减少,包括sentan-cilia apical structure protein(SNTN)和lactotransferrin(LTF)。重要的是,我们发现依那西普抑制NPC和LPS诱导中上调的靶点,如MMP-1,PTGS 2,可能还有MMP-3。我们的分析表明,鼻上皮屏障失调和适应不良的免疫反应是鼻咽癌发病机制的关键组成部分,沿着LPS诱导的组织损伤。
Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.
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