The prognostic value and response to immunotherapy of immunogenic cell death-associated genes in breast cancer

Rongling Zhao; Wenkang Wang; Limin Pan; Xuefeng Lv; Yi He; Wenping Lian; Yajie Ma; Xinyu Zhang; Ruijing Yu; Shuai Zhao; Xiaona Guo; Tao Huang; Mengle Peng

doi:10.3389/fonc.2023.1047973

The prognostic value and response to immunotherapy of immunogenic cell death-associated genes in breast cancer

Front Oncol. 2023 Feb 9:13:1047973. doi: 10.3389/fonc.2023.1047973. eCollection 2023.

Authors

Rongling Zhao¹, Wenkang Wang², Limin Pan³, Xuefeng Lv⁴, Yi He⁵, Wenping Lian¹, Yajie Ma⁶, Xinyu Zhang⁶, Ruijing Yu¹, Shuai Zhao¹, Xiaona Guo⁷, Tao Huang⁷, Mengle Peng¹

Affiliations

¹ Department of Clinical Laboratory, Henan No.3 Provincial People's Hospital, Zhengzhou, Henan, China.
² Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Breast Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
⁴ Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁵ Department of Mini-Invasive Spinal Surgery, Henan No.3 Provincial People's Hospital, Zhengzhou, China.
⁶ Department of Medical Affair, Henan No.3 Provincial People's Hospital, Zhengzhou, Henan, China.
⁷ Medical School, Huanghe Science and Technology University, Zhengzhou, Henan, China.

Abstract

Breast cancer (BRCA) remains the most prevalent cancer worldwide and the tumor microenvironment (TME) has been discovered to exert a wide influence on the overall survival and therapeutic response. Numerous lines of evidence reported that the effects of immunotherapy of BRCA were manipulated by TME. Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is capable of fueling adaptive immune responses and aberrant expression of ICD-related genes (ICDRGs) can govern the TME system by emitting danger signals or damage-associated molecular patterns (DAMPs). In the current study, we obtained 34 key ICDRGs in BRCA. Subsequently, using the transcriptome data of BRCA from the TCGA database, we constructed a risk signature based on 6 vital ICDRGs, which had a good performance in predicting the overall survival of BRCA patients. We also examined the efficacy of our risk signature in the validation dataset (GSE20711) in the GEO database and it performed excellently. According to the risk model, patients with BRCA were divided into high-risk and low-risk groups. Also, the unique immune characteristics and TME between the two subgroups and 10 promising small molecule drugs targeting BRCA patients with different ICDRGs risk have been investigated. The low-risk group had good immunity indicated by T cell infiltration and high immune checkpoint expression. Moreover, the BRCA samples could be divided into three immune subtypes according to immune response severity (ISA, ISB, and ISC). ISA and ISB predominated in the low-risk group and patients in the low-risk group exhibited a more vigorous immune response. In conclusion, we developed an ICDRGs-based risk signature that can predict the prognosis of BRCA patients and offer a novel therapeutic strategy for immunotherapy, which would be of great significance in the BRCA clinical setting.

Keywords: breast cancer; genes; immunogenic cell death; immunotherapy; prognosis.

Grants and funding

This study is funded by the Internal Scientific Project of Henan No.3 Provincial People’s Hospital (Grant No. HNSZSYKY220011), the Scientific and Technological Project of Henan province (Grant No. 2018020578) and 2022 joint construction project of Henan Medical Science and technology breakthrough plan (Grant No. LHGJ20220313).