Peripheral Blood IL-6 and STAT3 Gene Expression as Biomarkers Associated with Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancer: A Prospective Cross-Sectional Study

Kayhan Özdemir,1 Ali Muhtaroğlu,2 Muhammet Burak Kamburoğlu,3 Gamze Guney Eskiler,4 Zeynep Özman Gökçe,5 Belma Kocer6 1Department of General Surgery, Sakarya University Faculty of Medicine, Sakarya, Turkey; 2Department of General Surgery, Giresun University Faculty of Medicine, Giresun, Turkey; 3Department of General Surgery, Derince Training and Research Hospital, Kocaeli, Turkey; 4Department of Medical Biology, Sakarya University Faculty of Medicine, Sakarya, Turkey; 5Department of Medical Biochemistry, Bezmialem University Faculty of Medicine, İstanbul, Turkey; 6General Surgery Clinic, Private Beyhekim Hospital, Sakarya, TurkeyCorrespondence: Ali Muhtaroğlu, Department of General Surgery, Giresun University Training and Research Hospital, Aksu District, Mehmet Izmen Street, Number: 145, Giresun, PC, 28100, Turkey, Tel +90 506 314 64 41, Fax +90 454 310 20 02, Email [email protected]: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited targeted treatment options. Blood-based biomarkers that might help predict response to neoadjuvant chemotherapy (NAC) remain lacking. We examined whether pre-treatment peripheral blood expression of interleukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) was associated with clinicopathological features and NAC response in TNBC.Methods: This prospective cross-sectional study included 20 patients with TNBC and 10 healthy controls. Whole-blood RNA was isolated using Trizol, reverse-transcribed to cDNA, and analysed by RT-qPCR with TaqMan® Gene Expression Assays. Relative expression was calculated with the Livak (2−ΔΔCT) method using GAPDH as the housekeeping gene. Clinicopathological variables and pathological response assessed by the Miller–Payne system were analysed using IBM SPSS Statistics 23.0.Results: Compared with the control group, IL-6 and STAT3 expression levels were significantly elevated in patients with TNBC by 8.9-fold (p=0.001) and 25.1-fold (p=0.001), respectively. Higher levels of IL-6 and STAT3 expression were associated with adverse pathological features, including lymphovascular invasion, poor tumour differentiation, and reduced rates of complete pathological response. ROC analysis showed modest discriminatory performance for both markers. The AUC for IL‑6 was 0.68 (95% CI: 0.50– 0.86) and for STAT3 was 0.72 (95% CI: 0.53– 0.91).Conclusion: In this pilot cohort, higher peripheral blood IL-6 and STAT3 expression was associated with unfavourable clinicopathological features in TNBC. These findings suggest that the IL-6/STAT3 axis may have value within broader predictive biomarker panels, although larger prospective studies are needed before any clinical application is considered.Keywords: triple-negative breast cancer, IL-6, STAT3, gene expression, neoadjuvant chemotherapy, prognostic markers