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

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 dat...

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Main Authors: Xi Chen, Lijun Yan, Feng Jiang, Yu Lu, Ni Zeng, Shufang Yang, Xianghua Ma
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2021/4654302
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author Xi Chen
Lijun Yan
Feng Jiang
Yu Lu
Ni Zeng
Shufang Yang
Xianghua Ma
author_facet Xi Chen
Lijun Yan
Feng Jiang
Yu Lu
Ni Zeng
Shufang Yang
Xianghua Ma
author_sort Xi Chen
collection DOAJ
description 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.
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spelling doaj-art-4ca82b46e46546cf834e3216e38657c72025-02-03T01:25:16ZengWileyInternational Journal of Endocrinology1687-83371687-83452021-01-01202110.1155/2021/46543024654302Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical CarcinomaXi Chen0Lijun Yan1Feng Jiang2Yu Lu3Ni Zeng4Shufang Yang5Xianghua Ma6Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Hepatology, Nantong Third People’s Hospital Affiliated to Nantong University, Nantong 226000, ChinaDepartment of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaDepartment of Endocrinology, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, ChinaDepartment of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, ChinaDepartment of Endocrinology, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaAdrenocortical 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.http://dx.doi.org/10.1155/2021/4654302
spellingShingle Xi Chen
Lijun Yan
Feng Jiang
Yu Lu
Ni Zeng
Shufang Yang
Xianghua Ma
Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
International Journal of Endocrinology
title Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
title_full Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
title_fullStr Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
title_full_unstemmed Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
title_short Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma
title_sort identification of a ferroptosis related signature associated with prognosis and immune infiltration in adrenocortical carcinoma
url http://dx.doi.org/10.1155/2021/4654302
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