Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Abstract

Background: To classify triple-negative breast cancer (TNBC) immunotyping using the public database, analyze the differences between subtypes in terms of clinical characteristics and explore the role and clinical significance of immune subtypes in TNBC immunotherapy.Methods: We downloaded TNBC data from the cBioPortal and GEO databases. The immune genes were grouped to obtain immune gene modules and annotate their biological functions. Log-rank tests and Cox regression were used to evaluate the prognosis of immune subtypes (IS). Drug sensitivity analysis was also performed for the differences among immune subtypes in immunotherapy and chemotherapy. In addition, dimension reduction analysis based on graph learning was utilized to reveal the internal structure of the immune system and visualize the distribution of patients.Results: Significant differences in prognosis were observed between subtypes (IS1, IS2, and IS3), with the best in IS3 and the worst in IS1. The sensitivity of IS3 to immunotherapy and chemotherapy was better than the other two subtypes. In addition, Immune landscape analysis found the intra-class heterogeneity of immune subtypes and further classified IS3 subtypes (IS3A and IS3B). Immune-related genes were divided into seven functional modules (The turquoise module has the worst prognosis). Five hub genes (RASSF5, CD8A, ICOS, IRF8, and CD247) were screened out as the final characteristic genes related to poor prognosis by low expression.Conclusions: The immune subtypes of TNBC were significantly different in prognosis, gene mutation, immune infiltration, drug sensitivity, and heterogeneity. We validated the independent role of immune subtypes in tumor progression and immunotherapy for TNBC. This study provides a new perspective for personalized immunotherapy and the prognosis evaluation of TNBC patients in the future.

Immunogenic cell death-related classifications in breast cancer identify precise immunotherapy biomarkers and enable prognostic stratification

“…Initially, 21 confirmed ICD genes were studied, and 7 were found to be significantly associated with the survival and prognosis of patients with BC. Among them, the oncogenic genes were PIK3CA ( Hou et al, 2022 ; Ouedraogo et al, 2022 ), EIF2AK3 ( Chen et al, 2019 ), and MYD88 ( Chen et al, 2015 ), and the immune-related genes were ATG5 ( Park et al, 2022 ), HSP90AA1 ( Lin et al, 2020 ; Liu et al, 2021 ), IL1R1 ( Dagenais et al, 2017 ; Tulotta et al, 2021 ), and CD8A ( Hu et al, 2021 ), all of which have been found to be related to the occurrence and development of BC. Cho et al (2022) found using immunohistochemistry that PIK3CA mutations in patients with BC receiving adjuvant chemotherapy could cause poor survival and prognosis.…”

Integrating Genomic Information with Tumor-Immune Microenvironment in Triple-Negative Breast Cancer

“…The genes were downloaded from Illumina’s Biospace and Qiagen databases [ 30 , 31 ]. The list was further ascertained and supplemented by immune response genes used in comprehensive analysis of immunologic portraits of TNBC [ 32 , 33 ]. It is worth noting that reports on the analysis of immunologic portraits of TNBC [ 32 , 33 ] did not include information on somatic mutations.…”

“…The list was further ascertained and supplemented by immune response genes used in comprehensive analysis of immunologic portraits of TNBC [ 32 , 33 ]. It is worth noting that reports on the analysis of immunologic portraits of TNBC [ 32 , 33 ] did not include information on somatic mutations. In total, we evaluated a total of 1,751 immune-modulated genes.…”

Tumor Microenvironment Characterization in Breast Cancer and an Immune Cell Infiltration Score Development, Validation, and Application

“…Hu et al. ( 8 ) revealed that distinct immune phenotypes have different prognoses, gene mutations, immune infiltrations, and drug sensitivities in TNBC. Risom et al.…”