Serum IL2Rα as a Diagnostic Biomarker and Its Functional Interplay With IL-2 in Breast Cancer.
Breast cancer is a leading female malignancy, with chronic inflammation driving progression. The IL-2/IL-2R axis regulates immunity, but IL2RA's role in breast cancer (expression, diagnostic/prognostic value, and interplay with IL-2) is unclear.
A total of 252 consecutive patients (99 breast cancer and 153 benign breast disease) who received breast surgery were retrospectively analyzed. Serum cytokines were measured via electrochemiluminescence immunoassay; ROC, single-cell sequencing, and bioinformatics databases (TIMER and Kaplan-Meier plotter) were used to assess IL2RA/IL-2's utility and associations.
Serum IL2Rα was higher in breast cancer (336.9 vs. 275.8 U/mL, p < 0.001; no significant differences were observed for other cytokines). IL2Rα showed moderate diagnostic performance (AUC = 0.650, cut-off = 240.5 U/mL), correlated with NLR (p = 0.012), and showed a trend towards poor survival (p = 0.124, HR = 0.309, 95% CI: 0.069-1.381). Single-cell sequencing identified T cells as the primary source of IL2Rα in tumor tissues. High IL2RA expression strongly correlated with infiltration of immune cells, especially neutrophils (r = 0.673) and dendritic cells (r = 0.706). RNA-seq analysis showed IL2RA was upregulated in tumor tissues, associated with poor prognosis (p = 9.7e - 06, HR = 1.29, 95% CI: 1.15-1.44) and aggressive features (e.g., lymph node metastasis and HER2 positivity). In contrast, IL-2 was highly expressed in normal tissues, linked to better prognosis (p = 0.001, HR = 0.83, 95% CI: 0.74-0.93), and had opposing clinical correlations.
Serum IL2Rɑ could serve as a complementary auxiliary diagnostic biomarker for breast cancer, with associations with systemic inflammation, immune cell infiltration, and aggressive disease. The functional antagonism between IL2RA and IL-2 highlights the IL-2/IL2RA axis as a critical regulator of breast cancer pathophysiology, supporting its potential as a therapeutic target for improving breast cancer diagnosis and treatment.
A total of 252 consecutive patients (99 breast cancer and 153 benign breast disease) who received breast surgery were retrospectively analyzed. Serum cytokines were measured via electrochemiluminescence immunoassay; ROC, single-cell sequencing, and bioinformatics databases (TIMER and Kaplan-Meier plotter) were used to assess IL2RA/IL-2's utility and associations.
Serum IL2Rα was higher in breast cancer (336.9 vs. 275.8 U/mL, p < 0.001; no significant differences were observed for other cytokines). IL2Rα showed moderate diagnostic performance (AUC = 0.650, cut-off = 240.5 U/mL), correlated with NLR (p = 0.012), and showed a trend towards poor survival (p = 0.124, HR = 0.309, 95% CI: 0.069-1.381). Single-cell sequencing identified T cells as the primary source of IL2Rα in tumor tissues. High IL2RA expression strongly correlated with infiltration of immune cells, especially neutrophils (r = 0.673) and dendritic cells (r = 0.706). RNA-seq analysis showed IL2RA was upregulated in tumor tissues, associated with poor prognosis (p = 9.7e - 06, HR = 1.29, 95% CI: 1.15-1.44) and aggressive features (e.g., lymph node metastasis and HER2 positivity). In contrast, IL-2 was highly expressed in normal tissues, linked to better prognosis (p = 0.001, HR = 0.83, 95% CI: 0.74-0.93), and had opposing clinical correlations.
Serum IL2Rɑ could serve as a complementary auxiliary diagnostic biomarker for breast cancer, with associations with systemic inflammation, immune cell infiltration, and aggressive disease. The functional antagonism between IL2RA and IL-2 highlights the IL-2/IL2RA axis as a critical regulator of breast cancer pathophysiology, supporting its potential as a therapeutic target for improving breast cancer diagnosis and treatment.