FDX1 can Impact the Prognosis and Mediate the Metabolism of Lung Adenocarcinoma

Abstract

Background: Lung cancer has emerged as one of the most common cancers in recent years. The mitochondrial electron transport chain (ETC) is closely connected with metabolic pathways and inflammatory response. However, the influence of ETC-associated genes on the tumor immune response and the pathogenesis of lung cancer is not clear and needs further exploration.Methods: The RNA-sequencing transcriptome and clinical characteristic data of LUAD were downloaded from the Cancer Genome Atlas (TCGA) database. The LASSO algorithm was used to build the risk signature, and the prediction model was evaluated by the survival analysis and receiver operating characteristic curve. We explored the function of FDX1 through flow cytometry, molecular biological methods, and liquid chromatography–tandem mass spectrometry/mass spectrometry (LC–MS/MS).Results: 12 genes (FDX1, FDX2, LOXL2, ASPH, GLRX2, ALDH2, CYCS, AKR1A1, MAOB, RDH16, CYBB, and CYB5A) were selected to build the risk signature, and the risk score was calculated with the coefficients from the LASSO algorithm. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves of the dataset were 0.7, 0.674, and 0.692, respectively. Univariate Cox analysis and multivariate Cox regression analysis indicated that the risk signature is an independent risk factor for LUAD patients. Among these genes, we focused on the FDX1 gene, and we found that knockdown of FDX1 neither inhibited tumor cell growth nor did it induce apoptosis or abnormal cell cycle distribution. But FDX1 could promote the ATP production. Furthermore, our study showed that FDX1 was closely related to the glucose metabolism, fatty acid oxidation, and amino acid metabolism.Conclusion: Collectively, this study provides new clues about carcinogenesis induced by ETC-associated genes in LUAD and paves the way for finding potential targets of LUAD.

Pan-cancer analysis reveals the value of FDX1 as a novel biomarker in the prognosis and immunotherapy in human tumors

“…The above results are consistent with previous studies which proved that the expression levels of FDX1 in the tumor tissues of ACC, KICH, KIRC, KIRP [11] , LIHC [12] , and LUAD [10] were lower than those in the normal tissues.…”

“…FDX1 expression can promote the death of tumor cells [10] . What's more, the pathway that FDX1 induces tumor cell death has been illuminated in the recent research titled "Copper ionophore-induced cell death" published in the journal Science [17] .…”

“…More and more evidence suggests that FDX1 can promote the synthesis of various steroid hormones, and ATP production, and the knockdown of FDX1 significantly affected glucose metabolism, fatty acid oxidation, and amino acid metabolism [9] . Furthermore, the fact that the high expression of FDX1 contributes to the death of tumor cells by affecting the process of metabolism and suppressing the development of cancer has been confirmed in recent research [10][11][12][13] . Therefore, regulating the oxidative metabolism of the tumor microenvironment to inhibit the growth and promote the death of tumor cells by commanding the expressive level of FDX1 is of great significance for controlling the progress of cancer and strengthening the effect of immunotherapy.…”

A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma

“…FDX1 gene codes for a tiny iron-sulfur protein that transports electrons from NADPH to mitochondrial cytochrome P450 via ferredoxin reductase, which is implicated in the steroid, vitamin D, and bile acid metabolism. FDX1 may affect the prognosis of lung adenocarcinoma by mediating metabolism 21 . Lipoyltransferase 1 (LIPT1) is an enzyme that activates TCA cycle-associated 2-ketoacid dehydrogenases, and its deficiency inhibits the metabolism of the TCA cycle 22 .…”

Molecular Subtyping Based on Cuproptosis-Related Genes and Characterization of Tumor Microenvironment Infiltration in Kidney Renal Clear Cell Carcinoma

“…It has been shown that genetic polymorphisms in FDX1 are associated with IgA nephropathy in the Han Chinese population ( 10 , 11 ). In addition, recent studies have suggested that the FDX1 gene may play important roles in diseases such as lung adenocarcinoma ( 12 ) and polycystic ovary syndrome (PCOS) ( 13 ).…”