Integrative Omics Analysis Reveals Soluble Cadherin-3 as a Survival Predictor and an Early Monitoring Marker of EGFR Tyrosine Kinase Inhibitor Therapy in Lung Cancer

Abstract

Introduction: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit advanced lung adenocarcinoma (ADC) patients harboring activating EGFR mutations. We aimed to identify biomarkers to monitor and predict the progression of patients receiving EGFR-TKIs via a comprehensive omic analysis. Methods:We applied quantitative proteomics to generate the TKI resistance-associated pleural effusion (PE) proteome from ADC patients with or without EGFR-TKI resistance. Candidates were selected from integrated genomic and proteomic datasets. The PE (n=33) and serum (n=329) levels of potential biomarkers were validated with enzyme-linked immunosorbent assays (ELISAs). Western blotting was applied to detect protein expression in tissues, PEs and a cell line. Gene knockdown, TKI treatment and proliferation assays were used to determine EGFR-TKI sensitivity. Progression-free survival (PFS) and overall survival (OS) were assessed to evaluate the prognostic values of the potential biomarkers.Results: Fifteen proteins were identified as potential biomarkers of EGFR-TKI resistance. Cadherin-3 (CDH3) was overexpressed in ADC tissues compared to Research.

Identification of Six Prognostic Genes in EGFR–Mutant Lung Adenocarcinoma Using Structure Network Algorithms

“…In our study, it was also found to be overexpressed in EGFR-MT LUAD. Hsiao et al (2020b) found that CDH3 overexpression is related to the patients’ EGFR-TKI resistance, and reducing the expression level of CDH3 can increase the sensitivity of EGFR-TKI in patients. Moreover, sCDH3 was positively associated with the tumor stage in non–small-cell lung cancer, although it has not been found to have a significant effect on the prognosis in our study.…”

“…Although the other 5 hub genes in our study did not suggest significance for the OS of EGFR-MT LUAD patients, studies have confirmed that they are closely related to EGFR-MT LUAD metastasis, recurrence, and drug resistance. Ting et al found that high CDH3 expression is related to EGFR-TKI resistance ( Hsiao et al, 2020a ); Cao et al found that high CST1 expression can be used as a marker for recurrence and metastasis in patients with NSCLC ( Cao et al, 2015 ); Wang et al found that low expression of ZBTB16 can promote the survival of NSCLC tumor cells and enhance their invasiveness ( Wang et al, 2013 ; Xiao et al, 2015 ). Our study revealed that these genes are heavily enriched in metabolism-related biological processes such as the poly-N-acetyllactosamine biosynthetic process, glycosphingolipid biosynthesis—lacto and neglect series process.…”

Recurrence Risk of Liver Cancer Post-hepatectomy Using Machine Learning and Study of Correlation With Immune Infiltration

“…CDH3 has also been reported to be associated with prognosis in patients with colorectal adenocarcinoma and lung cancer. ( Xu et al, 2019 ; Hsiao et al, 2020 ). SELP is a member of the selectin family of cell adhesion molecules, and it mediates heterotypic aggregation of activated platelets to cancer cells and adhesion of cancer cells to stimulated endothelial cells.…”

MicroRNA‑665 regulates the proliferation, apoptosis and adhesion of gastric cancer cells by binding to cadherin 3

“…In the last three decades, several studies have reported the ability of CDH3 to accelerate the growth of multiple types of cancer, including lung (27), esophageal (9), colorectal (7) and breast cancer (28). A previous study has also suggested the involvement of CDH3 in promoting the motility of pancreatic cancer cells by activating Rho-family GTPases (8).…”