Di Sichen, Gong Min, Lv Jianmin, Yang Qiwei, Sun Ye, Tian Yijun, Qian Cheng, Chen Wenjin, Zhou Wang, Dong Keqin, Shi Xiaokai, Wang Yuning, Wang Hongru, Chu Jian, Gan Sishun, Pan Xiuwu, Cui Xingang
Department of Urinary Surgery, Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Yinchuan, Ningxia, China.
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
Cancer Cell Int. 2023 Aug 30;23(1):186. doi: 10.1186/s12935-023-03019-0.
Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC).
Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments.
It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4T cell Th1, CD8T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines.
Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.
肾细胞癌（RCC）是一种高代谢疾病。糖酵解信号的异常上调促进肿瘤生长，且糖酵解代谢与肾癌免疫治疗密切相关。本研究旨在确定糖酵解相关生物标志物TCIRG1是否以及如何影响透明细胞肾细胞癌（ccRCC）的有氧糖酵解、肿瘤微环境（TME）和恶性进展。
基于癌症基因组图谱（TCGA，n = 533）和来自MSigDB的糖酵解相关基因集，我们通过生物信息学分析鉴定了糖酵解相关基因TCIRG1，利用TIMER 2.0、UALCAN、LinkedOmics等在线数据库分析其在ccRCC中的免疫学特性，并通过体外实验观察其如何影响生物学功能和糖酵解代谢。
发现TCIRG1在ccRCC组织中的表达显著增加，且高TCIRG1表达与总体生存期（OS）差和无进展生存期（PFI）短相关。此外，TCIRG1表达与浸润免疫细胞高度相关，尤其是CD4T细胞Th1、CD8T细胞、NK细胞和M1巨噬细胞，且与PDCD1、CTLA4等免疫抑制剂、CCL5、CXCR3等趋化因子和趋化因子受体呈正相关。更重要的是，TCIRG1可能通过AKT/mTOR信号通路调节ccRCC中的有氧糖酵解，从而影响ccRCC细胞系的恶性进展。
我们的结果表明，糖酵解相关生物标志物TCIRG1通过影响ccRCC中的有氧糖酵解和肿瘤免疫微环境是一种肿瘤促进因子，这一发现可能为代谢干预和免疫治疗联合治疗ccRCC提供新思路。
