Abstract PO4-24-10: Prognostic role of SOX2 and STAT3 expression on circulating T lymphocytes and CD44+/CD24neg cells in the locally advanced and metastatic breast cancer

Abstract Introduction: Breast cancer (BC) is associated with a continuous increase in incidence, with high mortality rates in several countries. There are four immunophenotypes of BC, luminal A, luminal B, triple negative (TN), and HER2+. Some proteins in tumor cells and the tumor microenvironment are part of tumorigenesis and metastases. The CD44 molecule is considered an important marker of the inflammatory response. CD44 is present in all leukocytes and on the surface of tumor stem cells, involving tumor invasion and metastasis. Some authors have demonstrated that the signal transducer and activator of transcription 3 (STAT3) and sex-determining region Y-related group box 2 (SOX2) are related to the regulation of somatic cell division and tumorigenesis and metastasis in BC. Aim: To evaluate SOX2 and STAT3 expression on circulating T lymphocytes and CD44+/CD24neg cells in locally advanced and metastatic breast cancer. Methods: A cross-sectional study was conducted at the Hospital de Cancer de Pernambuco (HCP) and the Translational Research Laboratory of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) from March 2017 to April 2018. Sixty-five women diagnosed with breast cancer participated in this study, aged between 28 and 64. Of these, 51 women had stage III (locally advanced) breast tumors, and 14 with metastatic disease (stage IV). There were 24 healthy women aged 18 to 65 as a control group. The analysis of CD44, SOX2, and STAT3 expression was performed by flow cytometry. Results: elevated levels of CD44+/CD24neg cells and CD44+/CD24neg/SOX2+ cells were observed in the blood of BC patients with luminal B, HER2+, and TN compared to the control group (p< 0.0001). Low CD44+/CD24neg/STAT3+ levels in the patient's blood compared to the control group. Elevated CD44+/CD24neg and CD44+/CD24neg/STAT3+ cells were observed in locally advanced BC compared to metastatic group (p < 0.05). Patients with TNBC had elevated SOX2+T lymphocyte levels compared to luminal B and HER2+ subtypes groups (p< 0.05). HER2+ patients had low levels of T lymphocytes and SOX2+T cells compared to controls and luminal A groups (p < 0.05). High levels of total T cells (p=0.0007) and low SOX2+T lymphocytes (p=0.02) in locally advanced compared to metastatic disease (stage IV). Elevated levels of SOX2+T lymphocytes in patients with negative lymph nodes (N0) compared to N1 and N2 groups (p=0.004 and p < 0.0001, respectively). High levels of CD44+/CD24negSTAT3+ cells and T lymphocytes and low levels of STAT3+T lymphocytes in locally advanced TN subtype (stage III) compared to metastatic (stage IV). Conclusion: SOX2 and STAT3 expression on circulating T lymphocytes and CD44+/CD24neg cells in peripheral blood are prognostic roles in breast cancer. SOX2 and STAT3 expression are potential predictive biomarkers of disease progression in breast cancer regardless of tumor subtype. Investigating these biomarkers in peripheral blood has some advantages because peripheral blood collection is less invasive, easy to access, and allows evaluation at diagnosis, during treatment, and in cases of recurrence. Citation Format: Denise Viana, Victor Andrade, Marcelo Salgado, Carolina Vasconcelos, Leuridan Torres. Prognostic role of SOX2 and STAT3 expression on circulating T lymphocytes and CD44+/CD24neg cells in the locally advanced and metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-10.