Yang Yi-Fang, Yu Sung-Huan, Liao Jia-Bin, Lin Yu-Hsuan
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Institute of Precision Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Int J Med Sci. 2025 Jan 1;22(1):158-169. doi: 10.7150/ijms.101753. eCollection 2025.
Sinonasal inverted papilloma (SNIP) is characterized by a high recurrence rate and potential for malignant transformation. Although metabolic reprogramming plays a role in benign neoplasms, the specific metabolic pathways and biomarkers involved in SNIP pathogenesis remain unclear. RNA sequencing on paired SNIP and normal tissues identified altered genes with enzyme annotations and metabolic pathways by intersecting our cohort data (GSE270193, N=2) with the GSE193016 (N=4) dataset using Ingenuity Pathway Analysis. Functional and interaction assessments were performed using Metascape and STRING, with further validation via tissue microarray from an independent SNIP cohort (N=30). The estrogen biosynthesis pathway was significantly altered in both datasets. Five key biomarkers, AKR1B10, CYP1B1, CYP2C19, CYP3A5, and HSD17B13, were significantly altered in SNIP tissues. These markers, sharing Gene Ontology terms, showed significant correlations at both the transcript and protein levels. Functional analysis revealed enrichment in epithelial cell proliferation and regulation of EGFR signaling, suggesting a role in SNIP pathogenesis. Validation in an independent cohort confirmed elevated protein levels of these markers, all positively correlated with EGFR in SNIP tissues. Notably, AKR1B10, CYP2C19, and CYP3A5 exhibited specific expression patterns distinguishing SNIP from sinonasal squamous cell carcinoma. Altered estrogen biosynthesis signaling plays a role in SNIP pathogenesis, revealing distinct biomarkers that could serve as novel diagnostic markers and therapeutic targets for SNIP management.
鼻窦内翻性乳头状瘤（SNIP）的特点是复发率高且有恶变潜能。尽管代谢重编程在良性肿瘤中起作用，但SNIP发病机制中涉及的具体代谢途径和生物标志物仍不清楚。通过使用Ingenuity Pathway Analysis将我们的队列数据（GSE270193，N = 2）与GSE193016（N = 4）数据集相交，对配对的SNIP和正常组织进行RNA测序，确定了具有酶注释和代谢途径的改变基因。使用Metascape和STRING进行功能和相互作用评估，并通过来自独立SNIP队列（N = 30）的组织微阵列进行进一步验证。雌激素生物合成途径在两个数据集中均有显著改变。五个关键生物标志物AKR1B10、CYP1B1、CYP2C19、CYP3A5和HSD17B13在SNIP组织中显著改变。这些标志物共享基因本体学术语，在转录和蛋白质水平上均显示出显著相关性。功能分析显示在上皮细胞增殖和EGFR信号调节方面富集，提示其在SNIP发病机制中的作用。在独立队列中的验证证实了这些标志物的蛋白质水平升高，在SNIP组织中均与EGFR呈正相关。值得注意的是，AKR1B10、CYP2C19和CYP3A5表现出将SNIP与鼻窦鳞状细胞癌区分开来的特定表达模式。雌激素生物合成信号改变在SNIP发病机制中起作用，揭示了可作为SNIP管理的新型诊断标志物和治疗靶点的独特生物标志物。
