Bioinformatics analysis of CD۲۷۴ expression in triple negative breast cancer

Background and Aim: The immune system is active in breast cancer, playing a dual role in tumor progression and in immune surveillance. A major breakthrough in cancer immunotherapy was the discovery of immune checkpoint protein, which functions to effectively inhibit the immune system through various mechanisms. The first of such molecules is IL-۲ production and called cytotoxic T-lymphocyte associated protein ۴ (CTLA-۴). Other immune checkpoints that can be used as an inhibitory target is programmed cell death-۱ (PD-۱) T-cell receptor and its ligand found on many cancer cell, programmed death-ligand ۱ (PD-L۱), CD۲۷۴ gene. Infiltrating immune cells are both prognostic and predictive of response to standard breast cancer therapies. CD۲۷۴ encodes an immune inhibitory receptor ligand that is expressed by various types of tumor cells. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including breast cancer.Methods: Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression of CD۲۷۴ mRNA in different sub-types and stages of breast cancer and considered the survival rate extracted from the BRCA project data. The differential signature has been identified for a comprehensive and comparable search. The p value of ≤ ۰.۰۵ was considered statistically significant.Results: The CD۲۷۴ mRNA expression showed a significant over expression primary tumor compared to normal tissues. Also, the expression of CD۲۷۴ in stage III and IV was higher than Stage I, II. Among the different subclasses of breast cancer, triple-negative (TNBC) showed the overexpression of CD۲۷۴ (P-value ≤ ۰.۰۱). Among the triple-negative subclasses of breast cancer, TNBC immunomodulatory (TNBC- IM) (P-value =۰.۰۱) showed a significant increase in CD۲۷۴ expression. However TNBC mesenchymal (TNBC-M) showed significant CD۲۷۴ reduction. However, the Kaplan Mayer survival analysis did not show any significant difference between patients with different statues of CD۲۷۴ expression.Conclusion: : According to bioinformatics analysis, mRNA expression of CD۲۷۴ increases only in the TNBC subclass of breast cancer. Indeed, detailed analysis showed CD۲۷۴ overexpression in TNBC-IM subclass. This analysis suggests that CD۲۷۴ could be a diagnosis and prognosis marker in TNBC subclass of breast cancer.

Keywords:

Breast cancer , CD۲۷۴ , PD-L۱ , Immune checkpoint , BRCA