Hou Weiye, Fu Peiwen, Nie Zhenling, Wang Wanye, Li Jingjing, He Bangshun, Tang Qiao, Gao Tianyi
Department of Laboratory Medicine, Nanjing First Hospital, Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China.
Cancer Cell Int. 2025 Jul 28;25(1):285. doi: 10.1186/s12935-025-03917-5.
Septic disease usually results in delayed access to intensive care and poor outcomes in CRC patients. Studies have shown that T cells play important roles in CRC and sepsis immune systems. Hence, this study was performed to investigate the role of T cells and T-cell-related genes in CRC-related sepsis prognosis.
Single-cell sequencing data from CRC and sepsis patients were first analysed to explore common T-cell signals, including those related to cellular communication and signalling pathways. Then, functional enrichment analysis and Mendelian randomization (MR) analysis were conducted on marker genes of T cells to identify the key genes and their effects on septic CRC. The expression of key genes and their associations with CRC prognosis were validated in 32 blood samples from CRC patients with sepsis.
Compared with that in the negative control group, CD4_Naive cells infiltration was significantly lower in the combined single-cell sequencing data analysis of CRC and sepsis patients (p < 0.05). Our MR analysis and clinical sample verification results revealed that a high FMO4 gene was negatively associated with CD4_Naive cells infiltration and related to poor prognosis in septic patients with CRC (p < 0.05). The functional enrichment analysis of FMO4 revealed that FMO4 participated mainly in xenobiotic catabolic processes and taurine and hypo-Taurine metabolism in septic CRC, which further inhibited the energy metabolic activity of CD4_Naive cells.
The CD4_Naive cells related gene FMO4 appears to promote poor prognosis in septic CRC patients, suggesting that it is a promising candidate for therapeutic intervention.
脓毒症通常导致结直肠癌（CRC）患者进入重症监护的时间延迟且预后不良。研究表明，T细胞在CRC和脓毒症免疫系统中发挥重要作用。因此，本研究旨在探讨T细胞及T细胞相关基因在CRC相关脓毒症预后中的作用。
首先分析CRC和脓毒症患者的单细胞测序数据，以探索常见的T细胞信号，包括与细胞通讯和信号通路相关的信号。然后，对T细胞的标记基因进行功能富集分析和孟德尔随机化（MR）分析，以鉴定关键基因及其对脓毒症性CRC的影响。在32例CRC合并脓毒症患者的血样中验证关键基因的表达及其与CRC预后的关联。
在CRC和脓毒症患者的联合单细胞测序数据分析中，与阴性对照组相比，CD4幼稚细胞浸润显著降低（p < 0.05）。我们的MR分析和临床样本验证结果显示，高FMO4基因与CD4幼稚细胞浸润呈负相关，且与CRC脓毒症患者的不良预后相关（p < 0.05）。FMO4的功能富集分析表明，FMO4主要参与脓毒症性CRC中的异生物质分解代谢过程以及牛磺酸和低牛磺酸代谢，这进一步抑制了CD4幼稚细胞的能量代谢活性。
CD4幼稚细胞相关基因FMO4似乎促进了CRC脓毒症患者的不良预后，表明它是治疗干预的一个有前景的候选靶点。
