title: Decoding the EGFR mutation-induced drug resistance in lung cancer treatment by local surface geometric properties.
abstract: 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׳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.
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong, China. Electronic address: lichunma2-c@my.cityu.edu.hk.
authors.forename: Lichun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong, China.
authors.forename: Debby D
authors.initials: DD
authors.lastname: Wang
authors.affiliation: School of Computer Science and Technology, Soochow University, Suzhou, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Li Ka Sing Faculty of Medicne, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Wong
authors.affiliation: Li Ka Sing Faculty of Medicne, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Victor H F
authors.initials: VH
authors.lastname: Lee
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Alpha shape; Drug resistance; EGFR mutation; Lung cancer; Protein surface geometric properties; Solid angle