Identification and validation of neutrophils-related subtypes and prognosis model in triple negative breast cancer

Background: Neutrophils are considered to be crucial players in the initiation and progression of Cancer. However, the complex relationship between neutrophils and Cancer prognosis remains elusive, mainly due to the significant plasticity and diversity exhibited by these immune cells.

Methods: As part of our thorough investigation, we examined 38 Neutrophils-Related Genes (NRGs) and the associated copy number variations (CNV), somatic mutations, and gene expression patterns in relation to triple negative breast Cancer (TNBC). The interactions between these genes, their biological roles, and their possible prognostic significance were then examined. With the NRGs as our basis, we applied Lasso and COX regression analyses to create a predictive model for overall survival (OS). Furthermore, TNBC tissue and a public database were used to assess changes in MYO1D expression (MYO1D is characterized as a member of the myosin-I family, a group of motor proteins based on actin), its connection to neutrophil infiltration, and the clinical importance of MYO1D in TNBC.

Results: Four neutrophil-related genes were included in the development of a prognostic model based on neutrophils. The model was further shown to be an independent predicted factor for overall survival by multivariate COX regression analysis. According to this study, neutrophil subtype B as well as gene subtype B, were associated with activated Cancer immunity and poor prognosis of TNBC patients. Furthermore, considering that poor OS was linked to increased MYO1D expression, MYO1D was increased in TNBC tissues and associated with neutrophil infiltration. In vitro experiments also confirmed that MYO1D facilitates breast Cancer invasion and metastasis.

Conclusion: Based on the degree of gene expression linked to neutrophils, a unique prognostic model was created. MYO1D could be a potential prognostic biomarker in TNBC patients and also a prospective target for therapy.

Immunotherapy; Neutrophil; Triple-negative breast cancer; Tumor microenvironment; Tumor mutation burden.