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

Xi Chen,Feng Jiang,Yu Lu,Ni Zeng,Xianghua Ma,Shufang Yang,Lijun Yan,Giuseppe Reimondo

doi:10.1155/2021/4654302

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.

Highlights

Adrenocortical carcinoma (ACC) is a rare and aggressive malignant tumor derived from adrenal cortex with dismal prognosis [1]
To construct a ferroptosis risk signature and explore its prognostic value in ACC patients, a total of 94 overlapping ferroptosis-associated genes derived from the the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were preserved for further analysis. en, univariate Cox regression analysis was performed to assess the association between the expression levels of these 94 genes with ACC clinical survival information in the TCGA dataset
We found 31 ferroptosis-associated genes correlated with overall survival (OS) of ACC patients (Figure 1(a), p < 0.05)

Summary

Introduction

Adrenocortical carcinoma (ACC) is a rare and aggressive malignant tumor derived from adrenal cortex with dismal prognosis [1]. It is advantageous for ACC patients to receive complete surgical resection or treatment with mitotane, the 5-year survival rate is less than 40% [2, 3]. Prognosis varies based on age, scope of surgery, mitotic intensity, and hormone secretion. E present tumor, lymph node, and metastasis (TNM) classification method is unreliable in predicting prognosis owing to the heterogeneous features of ACC patients. It is challenging to make accurate prediction for ACC patients because of the diverse pathogenic factors, high heterogeneity, and poor prognosis. It is imperative to identify more effective biomarkers for predicting prognosis of ACC patients. Ferroptosis is a novel iron-dependent form of regulated cell death along with iron accumulation and lipid

Methods

Results

Conclusion