Assessing the Role of the Interleukin-12/STAT4 Axis in Breast Cancer by a Bioinformatics Approach

Interleukin-12 (IL-12) is an anti-tumor cytokine that promotes biological actions through the IL-12/STAT4 axis. Genetic variation and tumor microenvironment dynamics have been identified as critical elements for impaired immune anti-tumor responses. Breast cancer (BC) is a heterogeneous disease classified at the molecular level in several subtypes, each having unique biological and clinical traits. Despite research identifying the relevance of IL-12 in many cancer types, no studies have assessed the role of the IL-12/STAT4 axis in BC. The goal of this study was to evaluate the correlation of the IL-12/STAT4 signaling axis and BC patients' survival in general and in the context of the BC molecular subtypes. Bioinformatics analyses using TCGA data were completed to evaluate the correlation of the IL-12/STAT4 axis and BC. A high expression of important IL-12/STAT4 axis molecules such as the IL-12 receptor genes (IL12RB1 and IL12RB2), STAT4, IFNG and TBX21 were found to significantly increase BC patients' survival rates, especially in the most aggressive BC subtypes such as the luminal B (LumB), HER-2+ and basal like (BL). A possible relevant role of the IL-12/STAT4 axis in BC is suggested by this bioinformatics-study, which might also be subtype-specific. Further studies such as molecular and tumor microenvironment analyses will be required to clarify better the specific role of the IL-12 /STAT4 axis in BC. The results from these additional analyses may potentially improve IL-12-related immunotherapeutic approaches to BC.