Decoding the EGFR mutation-induced drug resistance in lung cancer treatment by local surface geometric properties

Epidermal growth factor receptor (EGFR) mutation-induced drug resistance leads to a limited efficacy of tyrosine kinase inhibitors during lung cancer treatments. In this study, we explore the correlations between the local surface geometric properties of EGFR mutants and the progression-free survival (PFS). The geometric properties include local surface changes (four types) of the EGFR mutants compared with the wild-type EGFR, and the convex degrees of these local surfaces. Our analysis results show that the Spearman[U+05F3]s rank correlation coefficients between the PFS and three types of local surface properties are all greater than 0.6 with small P-values, implying a high significance. Moreover, the number of atoms with solid angles in the ranges of [0.71, 1], [0.61, 1] or [0.5, 1], indicating the convex degree of a local EGFR surface, also shows a strong correlation with the PFS. Overall, these characteristics can be efficiently applied to the prediction of drug resistance in lung cancer treatments, and easily extended to other cancer treatments.