Clinicopathological and prognostic significance of SMAD4 in non-small cell lung cancer: A meta-analysis and database validation

Background:The relationship between SMAD family member 4 (SMAD4) and the clinicopathological and prognostic significance of non-small cell lung cancer (NSCLC) patients is unclear. Our aim was to investigate the association between SMAD4 expression and clinicopathological parameters and NSCLC prognosis. Methods:We searched articles in databases from inception to July 2022 to retrieve literature related to SMAD4 expression and the clinicopathological and/or prognostic significance of NSCLC patients. Odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. We evaluated the expression of SMAD4 and overall survival (OS) in NSCLC using the Kaplan-Meier plotter database. Results:Eight articles with 1461 NSCLC patients were included. SMAD4 expression was related to tumor differentiation (OR = 0.359, 95% CI: 0.238-0.543, P = .000), lymph node metastasis (OR = 0.469, 95% CI: 0.04-0.725, P = .001), tumor node metastasis stage (OR = 0.238, 95% CI: 0.156-0.362, P = .000) and good OS (HR = 0.592, 95% CI: 0.332-0.853, P = .000) in NSCLC. There was no significant association between SMAD4 expression and age (OR = 0.822, 95% CI: 0.515-1.312, P = .411) or sex (OR = 1.056, 95% CI: 0.675-1.653, P = .811). Furthermore, SMAD4 expression was lower in NSCLC, and a good prognosis in NSCLC (HR = 0.6, 95% CI = 0.51-0.72, P = 4.2 e-9) was shown to correlate with higher SMAD4 expression using the Kaplan-Meier Plotter database. Conclusion:SMAD4 expression is lower in NSCLC and correlated with lymph node metastasis, tumor differentiation, tumor node metastasis stage and good OS for NSCLC patients.

Automated summary

This study investigated the association between SMAD4 expression and clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC) patients. The results showed that SMAD4 expression was negatively correlated with tumor differentiation, lymph node metastasis, tumor node metastasis stage, and good overall survival (OS) in NSCLC. The study suggests that SMAD4 is expressed at lower levels in NSCLC and is associated with favorable prognosis.