In order to find a suitable biomarker to predict LNM involvement, we evaluated gene expression profiling studies and selected 20 genes (VANGL1, SMAD2, BUB1, EGFR, HES1, MAP2K1, NOTCH1, ANXA3, SMAD4, MTA1, LEF1, RHOA, TGF-ß, CD44, CD133, IL2RA, IL2RB, PITX2, PCSK7, and FOLH1) that play a key role in carcinogenesis, tumor growth, LNM development tumor invasion, and metastasis by regulating a variety of cellular processes (Table 1) [4,16,17,18,19,20]. This evidence concerns the gene SMAD4 and neoplasm.