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. 2022 Aug 19:13:962028.
doi: 10.3389/fgene.2022.962028. eCollection 2022.

Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer

Affiliations

Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer

Chen Xiao et al. Front Genet. .

Abstract

Background: Cancer is the second cause of death worldwide. Copperoptosis is a new mode of regulated cell death and is strongly associated with metabolic pathways. FDX1 is a key gene that promotes copperoptosis, and its impact on tumor pathogenesis and tumor immune response is indistinct and needs further exploration. Methods: Data was mined from the Cancer Genome Atlas database, the Broad Institute Cancer Cell Line Encyclopedia database, and the International Cancer Genome Consortium. Survival analyses included the Kaplan-Meier method for calculating the cumulative incidence of survival events and the log-rank method for comparing survival curves between groups. Immune cell infiltration levels were calculated using the Spearman correlation test and correlated with FDX1 expression to assess significance. More correlation analyses between FDX1 expression and mutational markers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), were also examined via Spearman assay to explore the relation between FDX1 expression and the sensitivity of common antitumor drugs VSports手机版. Results: FDX1 expression was downregulated in most kinds of cancers, and this high expression indicated better overall survival and death-specific survival. For several cancer types, FDX1 expression had a positive correlation with immune cell infiltration, and FDX1 also had a positive correlation with TMB and MSI in some cancer types, linking its expression to the assessment of possible treatment responses. Conclusion: The correlations between FDX1 expression and cancer in varioustissues, including clear links to cancer survival and prognosis, make FDX1 aninteresting biomarker and potential therapeutic target for cancer surveillance and futureresearch. .

Keywords: biomarkers; copperoptosis; immunological; pan-cancer; prognosis. V体育安卓版.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
mRNA expression levels of FDX1 from different tissue sources and tumors. (A) normal mRNA expression levels of FDX1 in various tissues from the GTEx database. (B) differences in FDX1 mRNA expression between tumor and peritumoral samples from the Cancer Genome Atlas database. Abbreviations: BLCA, bladder urothelial carcinoma; CESC, cervical and cervical cancer; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid tumor diffuse large B-cell lymphoma; ESCA, esophageal cancer; HNSC, head and neck squamous cell carcinoma; KIRP, renal papillary cell carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; PAAD, pancreatic cancer; PCPG, pheochromocytoma and paraneurysm; PRAD, prostate adenocarcinoma; reading, rectal adenocarcinoma; SARC, sarcoma; STAD, gastric adenocarcinoma; STES, gastric and esophageal cancer; TGCT, testicular germ cell tumor; THCA, thyroid cancer; THYM, thymoma; UCEC, endometrial cancer of the uterus; UCS, uterine carcinosarcoma.
FIGURE 2
FIGURE 2
Association of FDX1 mRNA expression levels with overall survival in multiple tumors from the Cancer Genome Atlas database. Cox regression analysis, p < 0.05 was evident.
FIGURE 3
FIGURE 3
Overall survival (OS) difference of high and low FDX1 mRNA expression groups in significantly prognostically relevant tumors from the Cancer Genome Atlas database (by median expression dichotomy). (A) OS difference of ACC groups. (B) OS difference between HNSC groups. (C) OS difference between KIRC groups. (D) OS difference of LGG groups. p < 0.05 was regarded significant, with a dashed line of 95% CI.
FIGURE 4
FIGURE 4
Correlation between FDX1 mRNA expression levels and disease-specific survival in multiple tumors from the Cancer Genome Atlas database. Cox regression analysis, p < 0.05 was evident.
FIGURE 5
FIGURE 5
Disease-specific survival (DSS) difference between high and low FDX1 mRNA expression groups in significantly prognostically relevant tumors from the Cancer Genome Atlas database (by median expression dichotomy). (A) DSS differences between adrenal cortical carcinoma groups. (B) DSS differences between KIRC groups. (C) DSS differences between groups in LGG. (D) DSS differences between thymoma groups. p < 0.05 was considered a significant, 95% CI dashed line.
FIGURE 6
FIGURE 6
Correlation of FDX1 expression with ESTIMATEScore score in pan-cancer.
FIGURE 7
FIGURE 7
Correlation of six immune cell (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) infiltration scores with FDX1 mRNA expression in six kinds of cancer [(A): BRCA, (B): IGG, (C): HNSC, (D): STAD, (E): KIRC, and (F): UCEC]. Spearman correlation test, p < 0.05 was significant.
FIGURE 8
FIGURE 8
Relation between FDX1 mRNA expression levels and mRNA expression at recognized immune checkpoints in multiple tumors from the Cancer Genome Atlas database. The lower triangle refers to the coefficients calculated by Pearson’s correlation test, and the upper triangle represents the p-value converted by log10. *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 9
FIGURE 9
Relationship between tumor mutational burden (TMB), microsatellite instability (MSI), and FDX1 mRNA expression levels in different tumors in the Cancer Genome Atlas database. TMB was calculated by the total mutation incidence per million base pairs in each tumor, and MSI was calculated by the total incidence of deletions or insertions per million base pairs of repeats. (A) correlation between TMB and FDX1 expression. (B) correlation between MSI and FDX1 expression. Spearman correlation test, p < 0.05 was evident.
FIGURE 10
FIGURE 10
Correlation graph with drug IC50. The correlation graph of gene and drug IC50 and the slope of the straight line are the correlation coefficients between gene and drug. [(A): chelerythrine, (B): ifosfamide, (C): everolimus, (D): ribavirin, (E): JNJ-42756493, (F): PX-316, (G): VE-821, (H): AZD-8055, (I): nelarabine, (J): vorinostat, (K): AMONAFIDE, (L): MK-2206, (M): avagacestat, and (N): ENMD-2076 precursor].

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