Prognostic impact of cancer stem cell markers on survival outcomes in solid tumors: A systematic review and meta-analysis.

Abstract

e15187 Background: Cancer stem cell (CSC) markers have been implicated in tumor aggressiveness and treatment resistance. Previous evidence suggests that high tumor expression of these CSC markers is associated with worse patient outcomes. However, their overall prognostic value for survival across solid tumors remains to be quantified. We aimed to systematically evaluate whether high expression of CD133, ALDH1, CD44, or SOX2 in solid tumors predicts poorer overall survival (OS). Methods: We performed a comprehensive literature search (Medline, Embase, Scopus, and Cochrane Library) for studies up to January 2026 that assessed immunohistochemical overexpression of CD133, ALDH1, CD44, or SOX2 in solid tumors and reported survival outcomes. Eligible studies were pooled using random-effects meta-analysis. Hazard ratios (HRs) or risk ratios for OS with 95% confidence intervals (CIs) were extracted or calculated. Heterogeneity and publication bias were assessed, and subgroup analyses were conducted by cancer type and marker. Results: Across included studies, high expression of each CSC marker showed a significant adverse impact on OS. Patients whose tumors overexpressed CD133 had substantially worse survival; for example, in non-small cell lung cancer high CD133 tripled the risk of 5-year mortality (RR ≈ 3.19) compared to low expression, and in head-neck cancers it was associated with ~2-fold higher hazard of death (HR ≈ 2.33). Overexpression of ALDH1 was likewise linked to poor outcomes, in colorectal cancer, high ALDH1 was associated with less than half the 5-year survival rate of low expressors (OR = 0.42, 95% CI 0.26–0.68). CD44 overexpression correlated with shorter survival as well, though effect sizes were more moderate (HR = 1.32, 95% CI 1.08–1.61 in colorectal cancer). Notably, CD44 positivity was still consistently indicative of worse prognosis across multiple tumor types (such as hepatocellular carcinoma and lung cancer). SOX2 overexpression also emerged as a significant negative prognostic factor: patients with SOX2-high tumors had markedly reduced survival (pooled HR ≈ 1.65, 95% CI 1.34–2.04) compared to SOX2-low patients. These associations held true in most subgroup analyses, although the magnitude of risk varied by cancer type. Conclusions: High tumor expression of CSC markers is significantly associated with worse overall survival in patients with solid tumors. This meta-analysis provides quantitative evidence that overexpression of these stemness-related markers portends poorer prognosis. Clinically, assessment of CSC marker status may help identify high-risk patients who could benefit from more aggressive therapy or novel treatments targeting CSCs. These findings underscore the prognostic value of CSC markers and support their further evaluation as biomarkers for risk stratification and as potential therapeutic targets in solid malignancies.