Oncology of Stem Cell Markers' Prognostic Functions in Oral Squamous Cell Carcinoma Patients Receiving Chemotherapy

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the global population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. Anti-EGFR-based therapies have limited success in OSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we studied prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) OSCC patients. Pretreatment tumour tissues of 404 HPV-negative LA-OSCCs patients and a subset of study were comparing cisplatin-radiation (CRT) and nimotuzumab plus cisplatin-radiation(NCRT). The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival (PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models. NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.69 (0.44–0.98)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.09–0.64); OS: HR (95% CI) = 0.39 (0.17–0.68)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. It was concluded that CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker.