Further proteogenomic, phosphoproteomic combine with functional experiments utilizing both primary tumor cells derived from patients and in vitro assays, illustrate the EGFR mutation-plus-amplification could not only lead to increase its cognate protein expression, but also strongly associates with increased ERK5 protein expression which could phosphorylate the PRPS1/2, activate nuclear biosynthesis pathway, and in turn might promote tumor cell proliferation and impact prognosis. The gene discussed is EGFR; the disease is neoplasm.