Different Pearson mutual-positive-correlation IGHD/BIK/EGFR/SPINK1/CCNA2-repressive molecular network was constructed from the overlapping of GRNInfer and Pearson under IGHD/BIK/EGFR/SPINK1/CCNA2 CC -0.25 in high lung adenocarcinoma compared with low human normal adjacent tissues, respectively. We propose IGHD inhibited DNA damage-induced inside-out cell differentiation through ENO1-SLC22A18-RECQL4-SQSTM1-PYCRL; BIK inhibiting axon guidance-induced membrane motility through BCC3-LGR4-DPY19L1-LIMK1; EGFR inhibited inflammatory immune-induced membrane development through CD180-TNFRSF17-POU2AF1; SPINK1 outside-inside-out inhibitive axon induced apoptosis through BUB1B-CCNA2-NCAPG-HIST1H2BD; CCNA2 inhibiting hypoxia, T cell and endocrine-induced cytoplasm differentiation through DPP41-DPP43-SLC2A5-TMEM63A-ENC12 in high lung adenocarcinoma based on integrative GO, KEGG, GenMAPP, BioCarta and disease databases. They are very useful to develop a new route and identify novel markers and potential drugs for prognosis and therapy for studying the pathogenesis