【摘要】 目的揭示卷曲相关蛋白(FRZB) mRNA表达在肺腺癌(LUAD)和肺鳞癌(LUSC)中潜在的临床应用价值和生物学作用。方法使用关键词"lung cancer"在隶属美国国家生物技术信息中心(NCBI)的基因表达综合数据库(GEO)中搜索相关数据,并且在癌症基因图谱数据库(TCGA)中下载肺腺癌和肺鳞癌数据。共8个肺腺癌和6个肺鳞癌数据集纳入研究。通过Cutoff Finder网站确定FRZB mRNA的临界值,并计算高、低表达组的风险比(HR)。结果肺腺癌患者癌组织中高表达FRZB mRNA具有更好的预后[单因素分析:HR(95%CI)=0.54(0.46～0.64),P<0.05;多因素分析:HR(95%CI)=0.66(0.54～0.79),P<0.05]。但在肺鳞癌中FRZB mRNA表达量对预后没有显著影响[单因素分析:HR(95%CI)=1.11(0.67～1.84),P>0.05;多因素分析:HR(95%CI)=1.13(0.71～1.78),P>0.05]。经过t-SNE和相关分析发现FRZB对WNT通路具有抑制作用。通过富集分析发现与FRZB相关基因富集于多条免疫相关通路,如补体系统、体液免疫等。结论高表达的FRZB mRNA对于肺腺癌具有更好的预后作用,其可能机制是通过抑制WNT信号通路实现。提示FRZB可作为一个潜在的肺腺癌预后良好标志物。更多还原

【Abstract】 Objective This study aimed to reveal the potential clinical and biological functions of frizzled related protein(FRZB) mRNA expression in lung adenocarcinoma(LUAD) and lung squamous cell carcinoma(LUSC). Methods We used the keyword "lung cancer" to search the data through Gene Expression Omnibus(GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA(The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio(HR). Results We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR(95%CI)=0.54(0.46-0.64),P<0.05 in univariate analysis; pooled HR(95%CI)=0.66(0.54-0.79),P<0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR(95%CI)=1.11(0.67-1.84),P>0.05 in univariate analysis; pooled HR(95%CI)=1.13(0.71-1.78),P>0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. Conclusion High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.更多还原