Youjiang Medical University for Nationalities Affiliated Hospital, Baise, Guangxi 533000, China.
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, Guangxi 541199, China.
Int J Biol Macromol. 2024 Aug;275(Pt 2):133618. doi: 10.1016/j.ijbiomac.2024.133618. Epub 2024 Jul 5.
There have been notable irregularities in CMTM6 expression observed in hepatocellular carcinoma (HCC), with an evident correlation between CMTM6 dysregulation and patient prognosis. The cell cycle progression came to a halt at the G2/M phase. In-depth RNA-sequencing analysis of CMTM6 knockdown Hep3B cells revealed that the most prominent effect of CMTM6 perturbation was on the expression of CXCL8, a chemokine involved in immune responses, particularly through the interleukin-17F (IL-17F) signaling pathway. By carefully examining the RNA-sequencing data obtained from CMTM6 knockdown Hep3B cells and cross-referencing it with the TCGA-LIHC database, we were able to discern that CMTM6 and programmed death-ligand 1 (PD-L1) collaboratively partake in immune regulation within T cells. Furthermore, CMTM6 exerted an influential role in modulating the infiltration of CD4+ and CD8+ T cells in the HCC microenvironment, thereby impacting the overall immune response. Our investigation found that HCC cases characterized by an elevated co-expression of CMTM6 and PD-L1, along with augmented CD4+ T cell infiltration, demonstrated comparatively longer overall and progression-free survival rates when contrasted with those displaying lower CD4+ T cell infiltration.
在肝细胞癌(HCC)中观察到趋化因子样因子超家族成员 6(CMTM6)表达存在明显异常,CMTM6 失调与患者预后有明显相关性。细胞周期在 G2/M 期停滞。对 CMTM6 敲低 Hep3B 细胞的深度 RNA 测序分析显示,CMTM6 扰动最显著的影响是对趋化因子 CXCL8 的表达,该趋化因子参与免疫反应,特别是通过白细胞介素 17F(IL-17F)信号通路。通过仔细检查从 CMTM6 敲低 Hep3B 细胞获得的 RNA 测序数据,并与 TCGA-LIHC 数据库交叉引用,我们能够发现 CMTM6 和程序性死亡配体 1(PD-L1)共同参与 T 细胞中的免疫调节。此外,CMTM6 在调节 HCC 微环境中 CD4+和 CD8+T 细胞浸润方面发挥了重要作用,从而影响整体免疫反应。我们的研究发现,与 CD4+T 细胞浸润较低的 HCC 病例相比,CMTM6 和 PD-L1 共同表达水平升高且 CD4+T 细胞浸润增强的 HCC 病例的总生存期和无进展生存期较长。