Breast cancer (BC) is the leading cause of death from tumors in women worldwide, influenced by various factors, including genetics. The T allele of the single nucleotide variant (SNV) rs3025039 at position +936 of the VEGFA gene has been reported to affect the mRNA regulatory mechanisms, potentially altering VEGFA expression and increasing BC risk. This study aimed to investigate the association between rs3025039 and BC in Mexican women residing in Jalisco, Mexico. The study included 231 women with a confirmed diagnosis of BC and 201 healthy subjects as a reference group (RG). PCR–RFLP was employed for the genotyping of rs3025039, with the visualization of amplified products using polyacrylamide gel electrophoresis. Significant differences were observed in rs3025039 alleles and genotypes between BC cases and the RG (p = 0.0038). The frequency of the T allele and the CT genotype was higher in the BC group compared to the RG, with a significant difference (p = 0.0006). In conclusion, this research suggests that the SNV rs3025039 is associated with a higher risk of BC in Mexican women. These findings enhance our understanding of the genetic underpinnings of BC in this population, offering potential insights for future studies and interventions.
Immunotherapy with antibodies targeting immune checkpoints, in combination with standard therapies, is one of the areas with the most significant clinical research, particularly in aggressive tumors such as triple-negative breast cancer, where there have been relevant advances with antibodies against PD-1/PD-L1. However, it is essential to define the biological and molecular factors that influence survival and response to immunotherapy, as other immune control points, such as CTLA-4, TIM-3, LAG-3, TIGIT, and VISTA, also play a role. The immune checkpoints were studied by microarrays and immunohistochemistry in 243 samples from patients with breast cancer, according to the molecular subtype. Significant differences in PD-1, PL-1, CTLA-4, and TIGIT expression were observed between triple-negative and Her-2 tumors compared to Luminal A and Luminal B tumors. No differences in VISTA expression were observed between the different molecular subtypes. Patients with high-grade tumors showed higher PD-1, PD-L1, LAG-3, and VISTA expression than low and intermediate-grade tumors. We observed a significant difference in PD-L1/TIGIT co-expression in tumor-infiltrating cells from patients with triple-negative tumors compared to patients with Luminal A, Luminal B, and Her2+ tumors. These results are relevant in the context of clinical application.
Breast cancer is the most common and deadliest cancer among women. While overexpression of specific markers guides disease stratification and has enabled the development of targeted therapies, identifying new therapeutic targets remains critical, particularly for aggressive subtypes lacking effective treatments. This study evaluated the expression of α-Lactalbumin (LALBA) and nucleolin (NCL) in breast cancer tissues from Mexican patients using gene expression analysis and immunohistochemistry. LALBA, a major milk protein normally expressed only during late pregnancy and lactation, was detected in nearly all tumor samples and showed higher levels in aggressive subtypes, with overexpression displaying a slight trend toward poorer overall survival. NCL, a multifunctional nucleolar protein, exhibited predominantly nuclear localization, with moderate expression associated with improved survival. Both proteins correlated with tumor immune features, including increased tumor-infiltrating lymphocytes (TILs) and PD-L1 expression for LALBA, and elevated CD8+ T cells, PD-L1, and TIM-3 expression for NCL. Overall, these findings suggest that LALBA and NCL are associated with tumor aggressiveness, immune context, and survival trends in breast cancer. Additional studies in larger cohorts are needed to define their clinical relevance.