长链非编码RNA LIN C00672与膀胱癌患者预后相关性及作用机制研究

Correlation and mechanism of long non-coding RNA LINC00672 with prognosis of patients with bladder urothelial carcinoma

目的探讨长链非编码RNA LINC00672与膀胱癌(BLCA)患者预后的相关性及作用机制。方法在TCGA数据库中得到差异表达基因LINC00672,并在TCGA数据库中验证LINC00672的表达以及与BLCA患者预后情况的相关性。用Cox回归法进行多因素分析,在此基础上构建列线图,进行内部验证。通过CTD数据库查询与LINC00672相关的治疗BLCA的化合物,并在PubChem数据库中探索这些相关化合物的结构。在TCGA数据库中分析LINC00672与免疫细胞之间的相关性,探讨可能的作用机制。结果LINC00672在BLCA肿瘤组织中的表达低于癌旁组织,而且LINC00672高表达的BLCA患者有更好的总生存期(OS)、疾病特异性生存期(DSS)和无铂化疗间期(PFI)。列线图C指数为0.649,预测模型具有一定的准确性。CTD数据库和PubChem数据库中得到9种与LINC00672相关的治疗BLCA的化合物。在TCGA数据库中发现LINC00672表达与大部分的免疫细胞的浸润水平均相关,同时,与PDCD1、CTLA4和CD274均有一定的负相关性。LINC00672可能通过参与磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)通路,mTOR通路,Hippo通路和Jak/stat通路来影响BLCA的生物学事件。结论LINC00672的表达升高可以延长BLCA患者的OS、DSS和PFI,可作为BLCA患者的新型预测性生物标志物,并在BLCA肿瘤微环境中对肿瘤细胞发生免疫逃逸可能起重要抑制作用。长链非编码RNA LINC00672能通过调节PI3K/AKT/mTOR通路促进膀胱癌进展,并与肿瘤免疫浸润相关。

Objective To investigate the relationship between long chain non-coding RNA LINC00672 and the prognosis of patients with bladder urothelial carcinoma(BLCA)and its potential mechanism.Methods The differentially expressed gene LINC00672 was obtained in the TCGA database,and the expression of LINC00672 and its correlation with the prognosis of BLCA patients were verified in the TCGA database.Cox law of return method was used to conduct multi factor analysis,and on this basis,a nomogram was constructed for internal verification.Query the compounds related to LINC00672 for the treatment of BLCA through the CTD database,and explore the structure of these related compounds in the PubChem database.Analyze the correlation between LINC00672 and immune cells in the TCGA database.Using GSEA enrichment analysis to explore possible mechanisms of action.Results The expression of LINC00672 in BLCA tumor tissue was lower than that in adjacent tissues,and BLCA patients with high expression of LINC00672 have betteroverall survival(OS),disease-specific survival(DSS)and platinum-free interval(PFI).The C-index of the line graph was 0.649,indicating that the prediction model has certain accuracy.Eleven compounds related to LINC00672 were identified in the CTD database and PubChem database for the treatment of BLCA.In the TCGA database,it was found that the expression of LINC00672 was correlated with the infiltration level of most immune cells,and had a certain negative correlation with PDCD1,CTLA4,and CD274.GSEA analysis suggests that LINC00672 may affect the biological events of BLCA by participating in the PI3K/protein kinase B pathway(AKT),mTOR pathway,Hippo pathway,and Jak/stat pathway.Conclusions The increased expression of LINC00672 can prolong the OS,DSS and PFI of BLCA patients,which can be used as a new predictive biomarker of BLCA patients,and may play an important role in inhibiting the immune escape of tumor cells in BLCA Tumor microenvironment.At the same time,we find that the long chain non coding RNA LINC00672 can promote the progression of bladder urothelial carcinoma by regulating the PI3K/AKT/mTOR pathway and is related to tumor immune invasion.