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. 2022 Jun 2;12:828999. doi: 10.3389/fonc.2022.828999

Table 2.

Summary of included studies that evaluate the epithelial–mesenchymal transition and immune cell markers with tumor budding in lung cancer.

Sr. no. Author/year/reference EMT and other molecular features Main findings
1 Yamaguchi, 2010 (23) β-catenin, E-cadherin, laminin 5γ2, EGFR, IGF-1R, CAIX, GLUT-1, Vimentin, Surfactant protein-A, TTF-1, MMP-7, CD68, and CD204 Reduced expression of E-cadherin, β-catenin, and surfactant protein-A and increased expression of laminin 5γ2 in tumor budding cells (p < 0.005).
No significant difference in CD44, growth factor receptor (EGFR and IGF-1R) hypoxia-induced protein (CAIX and GLUT-1), differentiation marker (TTF-1), MMP-7, and tumor-infiltrating macrophages (CD68 and CD204) between budding cells and near-budding cells.
2 Taira, 2011 (20) EMT markers and other markers E-cadherin (p = 0.004) and β-catenin (p = 0.002) levels in the tumor budding were significantly lower than solid nests.
Laminin-5γ2 expression level in the tumor budding was significantly higher than solid nests (p = 0.001).
Geminin-positive cells found more frequently in the TB cells than solid nests (median: 15 vs. 29; p = 0.008).
3 Kadota (2), 2015 (17) Infiltrative immune-cell markers KRAS and EGFR High-grade TB was significantly associated with high stromal CD3+ lymphocyte infiltration (p < 0.001), high stromal FoxP3+ lymphocyte infiltration (p < 0.001), high stromal FoxP3/CD3 risk index (p < 0.001), tumoral and stromal CD68 macrophage infiltration (p < 0.001), and tumoral IL-7R overexpression (p < 0.001).
High-grade tumor budding was more frequently identified in KRAS wild type tumors than mutated tumors (p = 0.038). Tumor budding was not significantly associated with EGFR mutation.
4 Kadota (3), 2017 (25) EMT markers Increased expression of vimentin in high-grade compared to low-grade tumor budding (p = 0.023).
Lower expression of E-cadherin was observed in the high-grade tumor budding in contrast to low-grade tumor budding (p = 0.003).
5. Ammour, 2017 (28) EMT markers Reduced expression of E-cadherin and a significant increase in nuclear ZEB1.

EMT, epithelial–mesenchymal transition.