The combination of NDUFS1 with CD4 + T cell infiltration predicts favorable prognosis in kidney renal clear cell carcinoma.

Frontiers in cell and developmental biology(2023)

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摘要
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.
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kidney renal,ndufs1
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