Background: Esophageal Squamous Cell Carcinoma (ESCC) presents a serious global health challenge, ranking among the most prevalent cancers worldwide. Small mothers against decapentaplegic 2 (SMAD2) and SMAD4 play a significant role in various types of cancer.

Methods: This study performed relative mRNA expression level profiling of SMAD2 and SMAD4 using Real time quantitative polymerase chain reaction (qPCR) in tissue and blood of ESCC patients and analyzed their associations with numerous clinical and lifestyle parameters for evaluating prognostic significance along with survival and hazard outcomes.

Results: SMAD2 and SMAD4 relative expression level showed downregulation in both tissue (85% and 87% respectively) and blood samples (80% and 79% respectively), and a significant positive correlation (p < 0.05) between their relative expression level was observed in both tissue and blood levels. Various clinicopathological parameters and food habits revealed significant association (p < 0.05) with SMAD2 and SMAD4 relative expression level. While analyzing survival and hazard in ESCC patients, various parameters revealed significant association (p < 0.05) in univariate model and histopathology grade, node stage, stage of metastasis, betel nut consumption, smoked food consumption and altered SMAD2 and SMAD4 relative expression level in tissue samples revealed significant association (p < 0.05) in the multivariate model, indicating their direct association with ESCC patients' survival and this makes them reliable predictors for ESCC prognosis.

Conclusions: This study's results revealed that downregulation of SMAD2 and SMAD4 is associated with poor prognosis and ESCC progression emphasizing their potential as potent prognostic factors for survival prediction as well as reliable biomarkers for screening.

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http://dx.doi.org/10.1007/s11033-025-10390-wDOI Listing

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