Machine learning immune-related gene based on KLRB1 model for predicting the prognosis and immune cell infiltration of breast cancer

Abstract

ObjectiveBreast cancer is a prevalent malignancy that predominantly affects women. The development and progression of this disease are strongly influenced by the tumor microenvironment and immune infiltration. Therefore, investigating immune-related genes associated with breast cancer prognosis is a crucial approach to enhance the diagnosis and treatment of breast cancer.MethodsWe analyzed data from the TCGA database to determine the proportion of invasive immune cells, immune components, and matrix components in breast cancer patients. Using this data, we constructed a risk prediction model to predict breast cancer prognosis and evaluated the correlation between KLRB1 expression and clinicopathological features and immune invasion. Additionally, we investigated the role of KLRB1 in breast cancer using various experimental techniques including real-time quantitative PCR, MTT assays, Transwell assays, Wound healing assays, EdU assays, and flow cytometry.ResultsThe functional enrichment analysis of immune and stromal components in breast cancer revealed that T cell activation, differentiation, and regulation, as well as lymphocyte differentiation and regulation, play critical roles in determining the status of the tumor microenvironment. These DEGs are therefore considered key factors affecting TME status. Additionally, immune-related gene risk models were constructed and found to be effective predictors of breast cancer prognosis. Further analysis through KM survival analysis and univariate and multivariate Cox regression analysis demonstrated that KLRB1 is an independent prognostic factor for breast cancer. KLRB1 is closely associated with immunoinfiltrating cells. Finally, in vitro experiments confirmed that overexpression of KLRB1 inhibits breast cancer cell proliferation, migration, invasion, and DNA replication ability. KLRB1 was also found to inhibit the proliferation of breast cancer cells by blocking cell division in the G1/M phase.ConclusionKLRB1 may be a potential prognostic marker and therapeutic target associated with the microenzymic environment of breast cancer tumors, providing a new direction for breast cancer treatment.

Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer

“…In the initial stage of tumor colonization or growth, the TME hinders the occurrence and development of tumors ( 24 ). However, the continuous stimulation of tumor antigens and immune activation responses results in the exhaustion or remodeling of the related effector cells in the TME, rendering them unable to perform physiological functions or promoting the malignant manifestations of tumors ( 25 ). The immune, stromal, and estimate scores were analyzed to evaluate the immune status of the three clusters.…”

A comprehensive analysis of the KLRB1 expression and its clinical implication in testicular germ cell tumors: A review

“…[ 12 , 31 ] KLRB1 is a possible prognostic marker and therapeutic target linked with human esophageal squamous cell carcinoma [ 17 ] and breast cancer tumors. [ 32 ] In this study, we examined the expression of KLRB1 in diverse pathological types of TGCTs by analyzing mRNA sequence data from 134 TGCTs patients in the TCGA database. In our study, we showed that KLRB1 was upregulated in tumor tissues, especially in seminomas, and that elevated KLRB1 expression correlated with adverse clinicopathological features of TGCT.…”

Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients

“…Moreover, SPARC secreted by CAFs promotes tumor growth by inhibiting adhesion of triple-negative BC cells whilst stimulating invasion and metastasis [19]. Recently, KLRB1 has become an increasing focus in tumor research as it has been associated with tumor progression [11][12][13][14][15]20]. Xu and Huang et al found that KLRB1 is a tumor suppressor gene involved in the BC progression.…”

“…Studies have shown that KLRB1 gene inactivation enhances T-cell-mediated killing of glioma cells in vitro and the anti-tumor function of KLRB1 in vivo [ 13 ], whereas decreased KLRB1 expression has been associated with poor prognosis in BC patients [ 11 ]. Xu and Huang et al found that KLRB1 is in the down-regulation trend in BC and a negative correlation between overexpression of KLRB1 and poor prognosis (such as overall survival (OS) and recurrence free survival (RFS)) of BC patients through survival analysis [ 14 , 15 ]. However, not much is known about the relationship between KLRB1 expression and BC subtypes (such as the BRCA) progression.…”