Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma

Abstract

Adrenocortical carcinoma (ACC) is a rare malignant tumor with poor prognosis. Ferroptosis, a new form of cell death, differs from other forms of cell death and plays a vital role in tumor progress. Our study aimed to establish a ferroptosis-related signature with prognostic value in ACC. RNA-seq data and corresponding clinical characteristics for ACC were downloaded from TCGA and GEO databases. Genes included in ferroptosis risk signature were assessed by univariable and multivariable Cox regression analysis as well as lasso regression analysis. The prognostic value of the ferroptosis risk signature was assessed using K-M and ROC curves. Furthermore, we performed GSEA to discover the enriched gene sets in high-risk group. Additionally, TIMER website was applied to detect a possible connection between the signature and immune cells infiltration. ssGSEA was performed to evaluate scores of immune cells and immune-related pathways in two groups. A ferroptosis signature comprised of six genes (SLC7A11, TP53, HELLS, ACSL4, PCBP2, and HMGB1) was constructed to predict prognosis and reflect the immune infiltration in ACC. Patients in high-risk group were inclined to have worse prognosis. The ferroptosis model performed well in predicting prognosis and could be served as an independent indicator in ACC. GSEA revealed that gene sets correlated with biological processes including cell cycle, DNA replication, base excision repair, and P53 signaling pathway were highly enriched in high-risk group. In addition, we discovered that the expressional levels of hub genes were linked to six immune cells’ infiltration in ACC tumor. ssGSEA revealed that contents of most immune cells significantly decreased in the high-risk group. In conclusion, the novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in ACC. It also brings us new insights into the possible value of targeting ferroptosis during the therapy of ACC.

Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM

“…However, clinical data show that only less than 10% of patients with GBM response to immunotherapy because of the low immunogenicity of GBM [ 10 , 48 ]. It has been shown that ferroptosis of cancer cells release high-mobility group box 1 (HMGB1) in an autophagy dependent manner [ 49 ], which increases the immunogenicity of cancer cells and promotes the maturation of DC cells [ 50 – 52 ]. The matured DC cells presents antigen to T lymphocytes and activates innate and adaptive immunity.…”

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

“…A study found that PCBP2 binding to severely oxidized RNA inhibited apoptosis induced by oxidative stress ( 78 ). Moreover, PCBP2 is one of the ferroptosis risk signature genes and can predict the prognosis of adrenocortical carcinoma in combination with the other five ferroptosis risk signature genes ( 79 ).…”

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer

“…Studies have shown that an FRG-based prognostic nomogram could improve the estimation of the survival rate of patients with clear cell renal cell carcinoma ( 50 ). Similarly, a novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in adrenocortical carcinoma ( 51 ). These analyses also suggested that the FS might be a potential and reliable prognostic biomarker in CC.…”