As shown in Figure 6D, our results reveal that the hypoxic tumor microenvironment exposed to xenobiotic toxicity nicotine and the dysfunction of genetic and epigenetic regulation could lead to dysregulation of IGF-1R and ITGB1 signaling pathway and the dysregulation of focal adhesion molecule TNS1 signaling, resulting in abnormal proliferation, ECM degradation, cell migration, and lymphangiogenesis to cause early stage LSCC to progress to middle stage LSCC. This evidence concerns the gene ITGB1 and neoplasm.