胰腺癌（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。在本研究中，我们研究了 PAAD 的线粒体融合相关基因，以建立用于 PAAD 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。采用最小绝对收缩和选择算子回归、cox回归、操作特征曲线以及cBioPortal数据库来评估模型性能，评估预后能力和敏感性。通过 CIBERSORT、QUANTISEQ 和 EPIC 比较免疫浸润水平。通过癌症数据库中的药物敏感性基因组学和“pRRophetic”R 软件包比较不同风险组之间的化疗敏感性。最后共有4个基因纳入多元Cox回归分析。风险预测签名构建为：(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一个独立的预后指标（P < .001，风险比[HR] = 1.870，95% CI = 1.568-2.232）。使用3种算法观察2个风险组中不同水平的免疫细胞浸润，包括肿瘤突变负荷（P = .0063）、肿瘤微环境评分（P = .01）以及肿瘤免疫功能障碍和排除评分（P = .01）。 0012）。化疗敏感性分析还显示，5-氟尿嘧啶 (P = .0127)、顺铂 (P = .0099)、多西他赛 (P < .0001)、吉西他滨 (P = .0047) 和紫杉​​醇的半最大抑制浓度(P < .0001)在高危组中较低，表明高危组患者对化疗的敏感性较高。总之，我们建立了一个由 4 个线粒体融合相关基因组成的基因签名板，以促进 PAAD 的早期诊断和预后预测。版权所有 © 2024 作者。由 Wolters Kluwer Health, Inc. 出版

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.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.