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Abstract：
Early detection of pancreatic adenocarcinoma (PAAD) remains a pressing clinical problem. Information on the clinical prognostic value of mitochondrial fusion-related genes in PAAD remains limited. In this study, we investigated mitochondrial fusion-related genes of PAAD to establish an optimal signature plate for the early diagnosis and prognosis of PAAD. The cancer genome atlas database was used to integrate the Fragments Per Kilobase Million data and related clinical data for patients with PAAD. Least absolute shrinkage and selection operator regression, cox regression, operating characteristic curves, and cBioPortal database was used to evaluate model performance, assess the prognostic ability and sensitivity. The levels of immune infiltration were compared by CIBERSORT, QUANTISEQ, and EPIC. Chemotherapy sensitivity between the different risk groups was compared by the Genomics of Drug Sensitivity in Cancer database and the \"pRRophetic\" R package. At last, a total of 4 genes were enrolled in multivariate Cox regression analysis. The risk-predictive signature was constructed as: (0.5438 × BAK1) + (-1.0259 × MIGA2) + (1.1140 × PARL) + (-0.4300 × PLD6). The area under curve of these 4 genes was 0.89. Cox regression analyses indicates the signature was an independent prognostic indicator (P < .001, hazard ratio [HR] = 1.870, 95% CI = 1.568-2.232). Different levels of immune cell infiltration in the 2 risk groups were observed using the 3 algorithms, with tumor mutation load (P = .0063), tumor microenvironment score (P = .01), and Tumor Immune Dysfunction and Exclusion score (P = .0012). The chemotherapeutic sensitivity analysis also revealed that the half-maximal inhibitory concentration of 5-fluorouracil (P = .0127), cisplatin (P = .0099), docetaxel (P < .0001), gemcitabine (P = .0047), and pacilataxel (P < .0001) were lower in the high-risk groups, indicating that the high-risk group patients had a greater sensitivity to chemotherapy. In conclude, we established a gene signature plate comprised of 4 mitochondrial fusion related genes to facilitate early diagnosis and prognostic prediction of PAAD.
摘要：
胰腺腺癌（PAAD）的早期检测仍然是一个紧迫的临床问题。关于PAAD中线粒体融合相关基因的临床预后价值的信息仍然有限。在这项研究中,我们研究了PAAD的线粒体融合相关基因，以建立PAAD的早期诊断和预后的最佳特征板。癌症基因组图谱数据库用于整合PAAD患者的每千碱基百万片段数据和相关临床数据。最小绝对收缩和选择算子回归，cox回归，工作特性曲线,并使用cBioPortal数据库评估模型性能，评估预后能力和敏感性。通过CIBERSORT比较免疫浸润水平，QUANTISER,和EPIC。通过癌症药物敏感性基因组学数据库和“pRophetic”R软件包比较了不同风险组之间的化疗敏感性。最后,共有4个基因纳入多变量Cox回归分析.风险预测特征构建为：（0.5438×BAK1）（-1.0259×MIGA2）（1.1140×PARL）（-0.4300×PLD6）。这4个基因的曲线下面积为0.89。Cox回归分析表明该特征是独立的预后指标（P<.001，风险比[HR]=1.870，95％CI=1.568-2.232）。使用3种算法观察2个风险组中不同程度的免疫细胞浸润,与肿瘤突变负荷（P=.0063），肿瘤微环境评分（P=0.01），和肿瘤免疫功能障碍和排斥评分（P=.0012）。化疗敏感性分析还显示，5-氟尿嘧啶的半数最大抑制浓度（P=0.0127），顺铂（P=0.0099），多西他赛（P<0.0001），吉西他滨（P=.0047），和帕拉他赛（P<0.0001）在高风险组中较低，表明高危组患者对化疗的敏感性更高。总之,我们建立了由4个线粒体融合相关基因组成的基因标签板，以促进PAAD的早期诊断和预后预测。
