The combination of NDUFS1 with immune infiltration predicts favorable prognosis in kidney renal clear cell carcinoma
作者单位：The Fourth Military Medical University
会议名称：《2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：kidney renal clear cell carcinoma NDUFS1 survival expression immune infiltration hsa-miR-320b
摘 要：Purpose: Kidney renal clear cell carcinoma(KIRC), the most common malignant tumor of the urinary system, is an immunogenic tumor, and KIRC patients therapeutic response and prognosis are relevant to immune infiltration. NDUFS1, the core subunit of mitochondria complex I(CI) in the respiratory chain, participating in the procedure of electron transport has been reported to be associated with the occurrence and development of tumors and be down-regulated in KIRC and associated with poor prognosis. However, the upstream regulator for NDUFS1 and their correlations with immune infiltration or patients survival remain unclear. Here, we tried to elucidate the immunological mechanism and clinical significance of NDUFS genes in KIRC.Methods: The expression of NDUFS genes in KIRC and their influences on patients survival were investigated by UALCAN, ENCORI(The Encyclopedia of RNA Interactomes), GEPIA(Gene Expression Profiling Interactive Analysis), Oncomine, TIMER(Tumor Immune Estimation Resource site) and Kaplan-Meier Plotter. MiR NAs regulating NDUFS1 in KIRC were predicted and analyzed by TargetScan and ENCORI. The correlations between NDUFS1 or miRNAs expression with immune cell infiltration or gene marker sets of immune infiltrates were analyzed via TIMER. The overall survival curves in high/low NDUFS1 or high/low hsa-miR-320 b expressed KIRC patients based on immune infiltration were analyzed via Kaplan-Meier Plotter.Results: From comprehensive bioinformatic analysis through digging into public online databases, we consistently found that in NDUFS gene family, NDUFS1 was significantly down-regulated in KIRC,high expression of NDUFS1, NDUFS4 predict good overall survival(OS) prognosis, and high expression of NDUFS1, NDUFS2, and NDUFS4 are correlated with good disease-free survival(DFS)prognosis. Moreover, the expression of NDUFS1 negatively correlates with advanced tumor grades and individual cancer stages, demonstrating that NDUFS1 may serve as a tumor suppressor gene in KIRC. NDUFS1 expression was positively correlated with infiltration of neutrophil and CD4+ T cells but negatively with NKT cell infiltrations. Furthermore, low NDUFS1 expression had a favorable survival in KIRC patients with enriched CD4+ T and neutrophil cell infiltration. In addition, 6 conserved miRNAs, including hsa-miR-599, hsa-miR-320 a, hsa-miR-320 b, hsa-miR-320 c, hsa-miR-320 d and hsa-miR-4429, were predicted to bind to the 3’ UTR region of NDUFS1 mR NA, among which only hsa-miR-320 b was highly expressed in KIRC and predicted poor survival. Hence, hsa-mir-320 b act as a possible negative regulator of NDUFS1. Most importantly, low NDUFS1 or high hsamiR-320 b consistently correlated to unfavorable outcomes in KIRC patients with decreased CD4+ T cell infiltration.Conclusion: Based on the comprehensive analysis of NDUFS genes expression in KIRC and their influence on prognosis, we found that NDUFS1 could be served as prognostic biomarkers for KIRC as reported previously. In addition, from the view of immunology and epigenetics, we have obtained a preliminary understanding of the possible functions and upstream regulator of NDUFS1 in KIRC.NDUFS1, a core protein of mitochondrial complex I, is negatively correlated with its down-regulator hsa-miR-320 b in KIRC. Both low NDUFS1 and high hsa-miR-320 b were connected with decreased CD4+T cell infiltration, and further with KIRC patients unfavorable outcomes. Our findings revealed that miRNA-mitochorial signatures could be a potential biomarkers for the optimal selection of patients with KIRC to immunotherapy.