Wu Dong, He Lin, Xu Zhe, Tian Ruo-Fei, Fan Xin-Yu, Fan Jing, Ai Jie, Bian Hui-Jie, Qin Wei-Jun, Qin Jun, Li Ling
National Translational Science Center for Molecular Medicine, Department of Cell Biology, School of Basic Medicine, The Fourth Military Medical University, Xi'an, China.
Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Front Cell Dev Biol. 2023 Jul 4;11:1168462. doi: 10.3389/fcell.2023.1168462. eCollection 2023.
Kidney renal clear cell carcinoma (KIRC) is an immunogenic tumor, and immune infiltrates are relevant to patients' therapeutic response and prognosis. , the core subunit of mitochondrial complex I, has been reported to be associated with KIRC patients' prognosis. However, the upstream regulator for and their correlations with immune infiltration remain unclear. The expression of genes in KIRC and their influences on patients' survival were investigated by UALCAN, ENCORI, Oncomine, TIMER as well as Kaplan-Meier Plotter. miRNAs regulating were predicted and analyzed by TargetScan and ENCORI. The correlations between expression and immune cell infiltration or gene marker sets of immune infiltrates were analyzed TIMER. The overall survival in high/low or hsa-miR-320b expressed KIRC patients with or without immune infiltrates were analyzed Kaplan-Meier Plotter. The combined NDUFS1 expression and/or CD4 T cell infiltration on KIRC patients' overall survival were validated by multiplexed immunofluorescence (mIF) staining in tissue microarray (TMA). Furthermore, the influences of NDUFS1 expression on the chemotaxis of CD4 T cells to KIRC cells were performed by transwell migration assays. We found that the low expression of mRNA and protein in KIRC was correlated with unfavorable patients' survival and poor infiltration of CD4 T cells. In patients with decreased CD4 T cell infiltration whose pathological grade less than III, TMA mIF staining showed that low expression of NDUFS1 had significantly poor OS than that with high expression of NDUFS1 did. Furthermore, hsa-miR-320b, a possible negative regulator of , was highly expressed in KIRC. And, low or high hsa-miR-320b consistently correlated to unfavorable outcomes in KIRC patients with decreased CD4 T cell infiltration. , overexpression significantly increased the chemotaxis of CD4 T cell to KIRC cells. Together, , upregulated by decreased hsa-miR-320b expression in KIRC patients, might act as a biomarker for CD4 T cell infiltration. And, the combination of NDUFS1 with CD4 T cell infiltration predicts favorable prognosis in KIRC.
肾透明细胞癌（KIRC）是一种免疫原性肿瘤，免疫浸润与患者的治疗反应和预后相关。线粒体复合物I的核心亚基已被报道与KIRC患者的预后相关。然而，其上游调节因子及其与免疫浸润的相关性仍不清楚。通过UALCAN、ENCORI、Oncomine、TIMER以及Kaplan-Meier Plotter研究了KIRC中该基因的表达及其对患者生存的影响。通过TargetScan和ENCORI预测并分析了调节该基因的微小RNA（miRNA）。利用TIMER分析该基因表达与免疫细胞浸润或免疫浸润基因标志物集之间的相关性。通过Kaplan-Meier Plotter分析高/低表达该基因或表达hsa-miR-320b的有或无免疫浸润的KIRC患者的总生存期。通过组织微阵列（TMA）中的多重免疫荧光（mIF）染色验证了该基因表达和/或CD4 T细胞浸润对KIRC患者总生存期的联合影响。此外，通过Transwell迁移试验研究了该基因表达对CD4 T细胞向KIRC细胞趋化性的影响。我们发现，KIRC中该基因mRNA和蛋白的低表达与患者不良生存及CD4 T细胞浸润不良相关。在病理分级小于III级且CD4 T细胞浸润减少的患者中，TMA mIF染色显示，该基因低表达患者的总生存期明显低于高表达患者。此外，hsa-miR-320b作为该基因可能的负调节因子，在KIRC中高表达。而且，低表达该基因或高表达hsa-miR-320b始终与CD4 T细胞浸润减少的KIRC患者的不良预后相关。该基因过表达显著增加了CD4 T细胞向KIRC细胞的趋化性。总之，在KIRC患者中，通过降低hsa-miR-320b表达而上调的该基因可能作为CD4 T细胞浸润的生物标志物。并且，该基因与CD4 T细胞浸润的联合可预测KIRC的良好预后。
