基于普通转录组和孟德尔随机分析探讨肾透明细胞癌中PANoptosis相关基因的诊断价值

Exploring the Diagnostic Value of PANoptosis-Related Genes in Kidney Renal Clear Cell Carcinoma Based on Common Transcriptome and Mendelian Randomization Analysis

肾透明细胞癌(KIRC)是一种常见的泌尿生殖系统恶性肿瘤,但其早期发现和诊断相当困难。泛凋亡(PANoptosis)强调细胞焦亡、细胞凋亡和坏死之间的作用和协调。本研究的目的是通过孟德尔随机分析方法(MR),确定PANoptosis相关基因(PRG)在KIRC中的作用,并揭示其因果关系。通过对3446个差异表达基因(DEGs)和347个PRGs进行交叉分析,我们发现66个差异表达的PANoptosis相关基因(DE-PRGs)存在表达量性状位点(eQTL)。分别进行双样本单变量和多变量MR分析后发现,PRF1 (P = 0.030,OR 95% 置信区间[CI] = 1.599 [1.047~2.441])、TNFRSF10B (P = 0. 008, OR 95% CI = 1.238 [1.058~1.447])、PDGFRB (P = 0.012, OR 95% CI = 0.546 [0.340~0.876])基因与KIRC疾病有关,以上3个标记基因同时存在时,PDGFRB基因是一个直接因素。此外,基于生物信息学分析,建立了具有良好诊断价值的KIRC模型。最后,通过数据分析和实时荧光定量PCR (RT-qPCR)验证标记基因的表达。

Kidney renal clear cell carcinoma (KIRC) is a common genitourinary malignancy, however, it is quite difficult to detect and diagnose at an early stage. PANoptosis emphasizes the role and coordination between pyroptosis, apoptosis and necroptosis. The aim of this study is to identify the role of PANoptosis-related genes (PRG) in KIRC and reveal their causal relationship by Mendelian randomization (MR) analysis. By intersecting 3446 differentially expressed genes (DEGs) and 347 PRGs obtained, we found that 66 differentially expressed-PANoptosis related genes (DE-PRGs) existed expression quantitative trait loci (eQTL). Two-sample univariate and multivariate MR analysis were performed respectively, and identified that causal relationships between PRF1 (P = 0.030, OR 95% confidence interval [CI] = 1.599 [1.047~2.441]), TNFRSF10B (P = 0.008, OR 95% CI = 1.238 [1.058~1.447]), PDGFRB (P = 0.012, OR 95% CI = 0.546 [0.340~0.876]) genes and KIRC disease, and the PDGFRB gene is a direct factor when the 3 marker genes were present simultaneously. Furthermore, model for KIRC with good diagnostic value were established based on bioinformatic analysis. Finally, the expression of marker genes was verified by data analysis and real-time fluorescence quantitative PCR (RT-qPCR).