背景:几种代谢紊乱和恶性肿瘤与异常的线粒体溶质载体家族25(SLC25A)成员活性直接相关。然而,其在胰腺癌(PC)中的生物学作用尚未完全了解。
方法:套索方法用于基于SLC25A成员创建新的PC预后风险模型,并探讨了其在肿瘤免疫学和能量代谢中的作用。此外,构建了SLC25A11、SLC25A29和SLC25A44的共表达网络。单细胞RNA测序(ScRNA-seq)揭示了PC中基因表达的分布。用TIMER数据库检查肿瘤免疫浸润。最后,研究了药物敏感性,并预测了共转录因子。
结果:在本研究中,基于SLC25A成员建立并验证了一种新的PC预后风险模型.与低危组相比,高危组的氧化磷酸化激活更低,免疫浸润表型更丰富。根据共表达网络研究,SLC25A11、SLC25A29和SLC25A44参与PC的能量代谢,阻止肿瘤生长,入侵,和转移。ScRNA-seq研究也指出了它们对肿瘤微环境的贡献。此外,大量免疫细胞的募集与SLC25A11和SLC25A44呈正相关,与SLC25A29呈负相关。此外,对20种食品和药物管理局批准的抗肿瘤药物的敏感性与上述基因密切相关,其中顺铂敏感性随着SLC25A29的上调而增加。最后,推测巩膜BHLH转录因子(SCX)和其他蛋白共同调节基因的mRNA转录.
结论:SLC25A成员对PC的肿瘤免疫和能量代谢至关重要,SLC25A11、SLC25A29和SLC25A44可作为预后标志物。这些标记的使用将提供新的方向来解开它们在PC中的作用机制。
Several metabolic disorders and malignancies are directly related to abnormal mitochondrial solute carrier family 25 (SLC25A) members activity. However, its biological role in pancreatic cancer (PC) is not entirely understood.
The lasso method was used to create a novel prognostic risk model for PC based on SLC25A members, and its roles in tumor immunology and energy metabolism were explored. Furthermore, co-expression networks were constructed for SLC25A11, SLC25A29, and SLC25A44. Single-cell RNA sequencing (ScRNA-seq) revealed the distribution of gene expression in PC. Tumor immune infiltration was examined with the TIMER database. Lastly, drug sensitivity was investigated, and co-transcriptional factors were predicted.
In the present study, a novel prognostic risk model was established and validated for PC based on SLC25A members. The high-risk group had a lower activation of oxidative phosphorylation and a more abundant immune infiltration phenotype than the low-risk group. According to co-expression network studies, SLC25A11, SLC25A29, and SLC25A44 were involved in the energy metabolism of PC and prevented tumor growth, invasion, and metastasis. ScRNA-seq research also pointed to their contribution to the tumor microenvironment. Moreover, the recruitment of numerous immune cells was positively correlated with SLC25A11 and SLC25A44 but negatively correlated with SLC25A29. Additionally, the sensitivity to 20 Food and Drug Administration-approved antineoplastic medicines was strongly linked to the aforementioned genes, where cisplatin sensitivity increased with the up-regulation of SLC25A29. Finally, the Scleraxis BHLH Transcription Factor (SCX) and other proteins were hypothesized to co-regulate the mRNA transcription of the genes.
SLC25A members are crucial for tumor immune and energy metabolism in PC, and SLC25A11, SLC25A29, and SLC25A44 can be used as favorable prognostic markers. The use of these markers will provide new directions to unravel their action mechanisms in PC.