Shang Chunliang, Huang Jiaming, Guo Hongyan
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2021 Jun 24;9:677831. doi: 10.3389/fcell.2021.677831. eCollection 2021.
The tumor metabolic reprogramming contributes to the progression and prognosis of cervical cancer (CC). However, the potential remodeling mechanisms of tumor metabolism in the immune microenvironment of CC remain largely unknown. In this study, we first performed microarray analysis to identify differential metabolic gene expression. A novel 5-metabolic-related genes (MRGs) signature comprising P4HA1, P4HA2, ABL2, GLTP, and CYP4F12 was established to better predict prognosis of CC using LASSO-Cox regression analysis. This signature could reveal the metabolic features and monitor the immune status of tumor microenvironment (TME). Among them, P4HA2 was significantly upregulated in CC tissues and negatively correlated with CD8+T cells. Knockdown of P4HA2 inhibited lipid droplets (LDs) accumulation and cancer cells invasion. Moreover, P4HA2 knockdown significantly suppressed PD-L1 expression. This study provides a new and feasible method for evaluating the prognosis of CC and explores the potential value to navigate metabolic pathways to enhance anti-tumor immunity and immunotherapy.
肿瘤代谢重编程促进宫颈癌(CC)的进展和预后。然而,CC免疫微环境中肿瘤代谢的潜在重塑机制仍 largely未知。在本研究中,我们首先进行微阵列分析以鉴定差异代谢基因表达。使用LASSO-Cox回归分析建立了一个由P4HA1、P4HA2、ABL2、GLTP和CYP4F12组成的新的5个代谢相关基因(MRGs)特征,以更好地预测CC的预后。该特征可以揭示代谢特征并监测肿瘤微环境(TME)的免疫状态。其中,P4HA2在CC组织中显著上调,且与CD8 + T细胞呈负相关。敲低P4HA2可抑制脂滴(LDs)积累和癌细胞侵袭。此外,敲低P4HA2可显著抑制PD-L1表达。本研究为评估CC的预后提供了一种新的可行方法,并探索了引导代谢途径以增强抗肿瘤免疫力和免疫治疗的潜在价值。