IL6 and neoplasm: To further investigate how signaling genes affect alterations in gene expression before and after the pre-transition state in the PI3K-Akt signaling pathway, the underlying molecular mechanism was unraveled based on the functional analysis of the COAD signaling gene pairs, as shown in Fig. 6C. In stage IIA and earlier stages, tumor cells were disordered and might have prompted critical transitions by cytokines (signaling genes), such as IL6, CSF3 and OSM, in the microenvironment.