Can Immunoexpression of Cancer Stem Cell Markers Prognosticate Tongue Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis

The objective was to evaluate the association of the immunoexpression of cancer stem cell (CSC) markers with clinicopathological and survival outcomes in tongue squamous cell carcinoma (TSCC) patients. This systematic review and meta-analysis [PROSPERO (CRD42021226791)] included observational studies that compared the association of clinicopathological and survival outcomes with CSC immunoexpression in TSCC patients. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were used as outcome measures. Six studies identified the association with three surface markers (c-MET, STAT3, CD44) and four transcription markers (NANOG, OCT4, BMI, SOX2). The odds of early-stage presentation were 41% (OR = 0.59, 95% CI 0.42–0.83) and 75% (OR = 0.25; 95% CI 0.14–0.45) lower in CSC and SOX2 immuno-positive cases than immuno-negative cases, respectively. The odds of well-differentiated tumors in transcription marker immuno-positive cases were 45% lower compared to immuno-negative cases (OR = 0.55, 95% CI 0.32–0.96). The odds of positive lymph nodes were 2.01 times higher in CSC immuno-positive cases compared to immuno-negative cases (OR = 2.01, 95% CI 1.11–3.65). Mortality in immuno-positive cases was 121% higher than that in immuno-negative cases (HR = 2.21; 95% CI 1.16–4.21). Advanced tumor staging and grading, lymph node metastasis, and mortality were significantly associated with positive immunoexpression of CSC markers.