背景:含纤维连接蛋白III型结构域3B(FNDC3B),含纤连蛋白III型结构域的蛋白质家族的成员,已在各种恶性肿瘤中显示。然而,FNDC3B在胰腺癌(PC)进展中的确切作用仍有待阐明.
方法:在本研究中,我们整合了国家生物技术信息中心的数据,癌症基因组图谱,基因型-组织表达数据库,和基因表达综合数据集分析FNDC3B表达及其与各种临床病理参数的关联。随后,基因本体论和京都基因和基因组百科全书,随着基因集富集分析(GSEA),单样品基因组富集分析(ssGSEA)和估计分析被招募以深入研究基于FNDC3B表达的生物学功能和免疫浸润。此外,采用Cox分析和Kaplan-Meier分析进行预后评估.随后,根据Cox分析结果构建列线图以增强FNDC3B的预后能力。最后,初步探讨了FNDC3B在PC细胞中的生物学功能。
结果:研究表明,与正常胰腺组织相比,FNDC3B在肿瘤组织中的表达明显更高,这种表达与各种临床病理参数显着相关。GSEA揭示了FNDC3B参与与整合素信号通路和细胞粘附相关的生物过程和信号通路。此外,ssGSEA分析显示FNDC3B表达与Th2细胞和中性粒细胞浸润呈正相关,而与浆细胞样树突状细胞和Th17细胞浸润呈负相关。Kaplan-Meier分析进一步支持PC患者中FNDC3B高表达与较短的总生存期有关。疾病特异性生存,和无进展间隔。然而,尽管单因素分析显示FNDC3B表达与PC患者预后之间存在显著相关性,这种关联在多变量分析中不成立.最后,我们的发现强调了FNDC3B表达在调节增殖中的关键作用,迁移,和PC细胞的侵袭能力。
结论:尽管存在局限性,这项研究的结果强调了FNDC3B作为预后生物标志物的潜力及其在推动PC进展中的关键作用,特别是在协调免疫反应方面。
BACKGROUND: Fibronectin type III domain containing 3B (FNDC3B), a member of the fibronectin type III domain-containing protein family, has been indicated in various malignancies. However, the precise role of FNDC3B in the progression of pancreatic cancer (PC) still remains to be elucidated.
METHODS: In this study, we integrated data from the National Center for Biotechnology Information, the Cancer Genome Atlas, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets to analyze FNDC3B expression and its association with various clinicopathological parameters. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, along with Gene Set Enrichment Analysis (GSEA), single sample Gene Set Enrichment Analysis (ssGSEA) and estimate analysis were recruited to delve into the biological function and immune infiltration based on FNDC3B expression. Additionally, the prognostic estimation was conducted using Cox analysis and Kaplan-Meier analysis. Subsequently, a nomogram was constructed according to the result of Cox analysis to enhance the prognostic ability of FNDC3B. Finally, the preliminary biological function of FNDC3B in PC cells was explored.
RESULTS: The study demonstrated a significantly higher expression of FNDC3B in tumor tissues compared to normal pancreatic tissues, and this expression was significantly associated with various clinicopathological parameters. GSEA revealed the involvement of FNDC3B in biological processes and signaling pathways related to integrin signaling pathway and cell adhesion. Additionally, ssGSEA analysis indicated a positive correlation between FNDC3B expression and infiltration of Th2 cells and neutrophils, while showing a negative correlation with plasmacytoid dendritic cells and Th17 cells infiltration. Kaplan-Meier analysis further supported that high FNDC3B expression in PC patients was linked to shorter overall survival, disease-specific survival, and progression-free interval. However, although univariate analysis demonstrated a significant correlation between FNDC3B expression and prognosis in PC patients, this association did not hold true in multivariate analysis. Finally, our findings highlight the crucial role of FNDC3B expression in regulating proliferation, migration, and invasion abilities of PC cells.
CONCLUSIONS: Despite limitations, the findings of this study underscored the potential of FNDC3B as a prognostic biomarker and its pivotal role in driving the progression of PC, particularly in orchestrating immune responses.