Tumor Budding in Upper Gastrointestinal Carcinomas: A Systematic Review and Meta-Analysis.

Gastrointestinal (GI) carcinomas represent a heterogeneous composition of malignancies that stem from the organs of the GI tract. They are among the most prevalent and are associated with high mortality alongside morbidity rates. This study utilized the guidelines set forth by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), whereby four medical databases were searched for relevant scholarly publications published between 2010 and 2024. These databases were PubMed, Web of Science, and ScienceDirect. Risk of bias (RoB) for cohort, case-controlled, and cross-sectional studies was assessed using the Newcastle-Ottawa Scale (NOS), whereas randomized controlled trials (RCTs) used the Cochrane (RoB) tool. With the assumption that the observed estimate of the treatment effect differs between the included studies, a random effect meta-analysis was carried out. In the meta-analysis, fifteen trials with 7607 patients were considered. The findings indicate a substantial correlation between high-grade tumor budding and tumor stage, (χ²=480472.97, P<0.00001) with a mean difference of -6.18 at 95% confidence interval (95% CI) (-14.66 to 2.30), tumor differentiation (χ²=23.31, P<0.00001) with a mean difference of -12.60 at 95% CI (-35.89 to 10.68), lymph vascular invasion (χ²=29.59, P<0.00001) with a mean difference of -5.03 at 95% CI (-11.26 to 1.21), and lymph node metastasis (χ²​​​​​​​=158.30, P<0.00001) with a mean difference of -3.44 at 95% CI (-4.72, -1.78). Furthermore, in upper gastrointestinal (UGI) patients, high-grade tumor budding was associated with a negative five-year overall survival (P<0.00001) and a mean difference of -0.09 at 95% CI (-0.20 to 0.02). In regards to the risk of bias, most of the retrospective, prospective, case-control, and cohort studies 10/14 were of satisfactory quality. Moreover, 5/7 of the clinical trials had a low risk of bias. However, the funnel plot indicated that there is a probability of publication bias in favor of tumor budding. The study revealed a significant link between tumor budding and key prognostic factors-overall survival, lymph node metastasis, tumor differentiation, and lymphovascular invasion-in upper gastrointestinal carcinomas. High-grade tumor budding is associated with poor clinicopathological characteristics and a five-year overall survival. Tumor budding may serve as a unique prognostic marker. To confirm these results, further research with larger preoperative UGI biopsies is recommended.