FOXP3 Expression as a Biomarker in Metastatic Colorectal Cancer Treated with Irinotecan-based Therapy

Background: Forkhead box protein 3 (FOXP3) is one component of the colorectal tumor microenvironment had a crucial role in development of metastases and progression. Our study aims to investigate the role of FOXP3 as a prognostic biomarker in metastatic colorectal cancer (mCRC) patients received second line therapy (irinotecan-based chemotherapy in combination with anti-EGFR or anti-VEGF, when indicated).
Methods: The study included 53 patients with mCRC treated with irinotecan-based chemotherapy with anti-EGFR or anti-VEGF. FOXP3 was assessed by immunohistochemistry. We use the median of FOXP3 score as the cutoff value of its expression. We evaluate the correlation between the expression of FOXP3, response to therapy, and survival of the patients.
Results: Out of total 53 patients, about half of the cases had rectal site of primary tumor (52.83%). Most of them had T3 or T4 tumor (90.57%), positive nodal disease (79.25%), high tumor grade (84.91%) and synchronous metastases (60.37%). Approximately half of the patients (49.18%) had high FOXP3 expression while the other (50.91%) had a low expression.
There is a clinical significance of higher overall response rate (15.4% vs. 11.1%) and disease control rate (42.3% vs. 33.3%) in favor of high FOXP3 expression, but of statically insignificance.
Interestingly, high FOXP3 expression in mCRC patients was associated with significantly longer median progression-free survival compared with those having low FOXP3 expression (5.55 months vs. 3.71 months; P= 0.036). Also, there was a significant prolongation of 9.69 months in median overall survival in favor of patients with high FOXP3 expression (14.98, 95%CI: 11.96-18.00months vs. 5.29, 95%CI: 4.02-6.56 months; P= 0.045).
Conclusion: FOXP3 is a potential good prognostic marker in mCRC patients receiving irinotecan-based chemotherapy with target therapy, when indicated. This is a promising marker that may be incorporated into the prognostic panel for these patients.