The Ohio State College of Medicine, Columbus, Ohio, United States of America.
Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, United States of America.
PLoS One. 2021 Oct 14;16(10):e0258187. doi: 10.1371/journal.pone.0258187. eCollection 2021.
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.
鼻咽癌（NPC）是一种上皮来源的癌症，在某些人群中的发病率较高。虽然 NPC 采用同期放化疗的治愈率较高，但复发率较高，且治疗的下游发病率较高。因此，寻找替代疗法迫在眉睫。
我们使用 Search Tag Analyze Resource（STARGEO）平台，通过美国国立生物技术信息中心（NCBI）的基因表达综合数据库（GEO）进行荟萃分析，以确定 NPC 的发病机制。我们从 NPC 公共患者数据中确定了 111 个肿瘤样本和 43 个健康鼻咽上皮样本。我们使用 IPA 分析相关特征，限制基因的表达在疾病和对照样本之间具有统计学意义（p<0.05）和绝对实验对数比大于 0.15。
我们的荟萃分析确定 LPS 诱导的组织损伤在 NPC 组织中被激活。此外，白细胞介素-1（IL-1）和 SB203580 是顶级上游调节剂。肿瘤发生相关基因，如同源盒 A10（HOXA10）和前列腺素内过氧化物合酶 2（PTGS2 或 COX-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）也被上调。编码与维持健康鼻呼吸上皮结构完整性相关的蛋白质的基因表达下调，包括纤毛尖端结构蛋白（SNTN）和乳铁蛋白（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、PTGS2 和可能的 MMP-3。
我们的分析表明，鼻上皮屏障失调和适应性免疫反应是 NPC 发病机制的关键组成部分，以及 LPS 诱导的组织损伤。
