Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) is a main subtype of kidney cancers. Cuproptosis and ferroptosis are correlated with immune infiltration and prognosis in tumors. However, the role of Cuproptosis-related Ferroptosis genes (CRFGs) in KIRC has rarely been fully understood. Therefore, we constructed a prognostic signature based on different expression of CRFGs in KIRC. All raw data of this study were extracted from public TCGA datasets. Cuproptosis and Ferroptosis genes were collected from the previous research. Finally, a total of 36 significantly different CRFGs were identified from TCGA–KIRC cohort. Six-gene signature (TRIB3, SLC2A3, PML, CD44, CDKN2A and MIOX) was identified by LASSO Cox regression based on the significantly different CRFGs. The CRFGs signature was correlated with worse overall survival and the AUC was 0.750. Functional enrichment indicated that CRFGs were mainly enriched in metabolism, drug resistance, tumor immunity pathways. Besides, the IC50 and immune checkpoint differentially expressed between different groups. The proposed 6-CRFGs signature is a promising biomarker to predict clinical outcomes and therapeutic responses for KIRC patient.

PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma

“…In this work, it was also observed that PML is downregulated at the protein level in ccRCC specimens compared to matched normal tissue (Lin et al, 2014 ). In contrast with these findings, recent studies found that PML is overexpressed in ccRCC and belongs to prognostic high-risk signatures (Li et al, 2019 ; Luo et al, 2023 ), thus pointing to an oncogenic function. Our work confirms that PML is upregulated in ccRCC (at the mRNA and protein level) in tissues and cell lines, thus implying that previously reported evidence of PML downregulation (Lin et al, 2014 ) may be due to patients’ selection or use of a specific antibody for immunohistochemical studies.…”

“…It was recently reported that PML is overexpressed in ccRCC compared to normal kidneys and belongs to a high-risk gene signature associated with worse outcome (Wu et al, 2023 ; Luo et al, 2023 ; Wang et al, 2023 ; Li et al, 2019 ). To determine if the PML protein is overexpressed cell-autonomously within ccRCC cells, we compared PML expression in ccRCC cell lines (Caki-1, RCC4, A49786-O and the patient-derived xenograft cell line UTSW-XP258, hereafter referred to as XP258) (Elias et al, 2021 ) with breast cancer (MDA-MB-231, MDA-MB-468, MCF7) and glioblastoma (U87) cell lines, as representative of tumor types where PML is reportedly overexpressed (Carracedo et al, 2012 ; Martín-Martín et al, 2016 ; Ponente et al, 2017 ; Amodeo et al, 2017 ; Aldaz et al, 2022 ; Kuwayama et al, 2009 ; Iwanami et al, 2013 ; Tampakaki et al, 2021 ).…”

“…In a study investigating the role of the SCP1 phosphatase, which promotes PML degradation, it was suggested that PML exerts tumor-suppressive functions in ccRCC (Lin et al, 2014 ). However, more recent studies reported that PML is overexpressed in ccRCC and belongs to gene signatures that identify high-risk patients and correlate with worse disease outcome (Wu et al, 2023 ; Luo et al, 2023 ; Wang et al, 2023 ; Li et al, 2019 ), implying oncogenic activities. Beside this correlative evidence however, a rigorous functional assessment of the involvement of PML in this disease is still lacking.…”

Construction of exosome-related genes risk model in kidney cell carcinoma predicts prognosis and immune therapy response

“…The same analyses were performed in another two external validation cohorts, and the results proved to be the same trends (Figure 6B, 6C; Supplementary Figure 6B, 6C). We then compared our PRERG signature with nine other risk signatures [24][25][26][27][28][29][30][31][32]. PRERGs risk signature showed the top 3 of AUC for 3-/5-/7-year prognosis of the KIRC patients (Supplementary Figure 7A-7C), indicating that our risk signature has a higher predicted accuracy.…”