Next, we made an effort to identify the potential signaling pathways that might exist among the DEPs using KEGG pathway analysis, an extensively used method for the integration and interpretation of high-throughput proteomic and genomic data.35,46,47 We found that the DEPs were related to multitudinous signaling pathways. The top five pathways containing ≥4 DEPs included the viral infectious disease pathway, which is involved in eight proteins AKT2, IFIT1, RSAD2, NFYB, ANAPC7, COL4A1, Mx1, and ISG15; the signal transduction pathway, which is involved in six proteins AKT2, BNIP3, PDK1, WDR24, TMEM55B, and COL4A1; the immune system pathway, which is involved in four proteins ISG15, IFIT1, OAS1 and IFIT3; the digestive system pathway, which is involved in four proteins AKT2, MT-2A, COL4A1, and cystatin C; and the cancer pathway, which is involved in four proteins PDK1, AKT2, COL4A1, and CDK9. Once again, we found that the same protein can participate in different signaling pathways. For instance, ISG15, a IFN-α-inducible protein that is paramount to the host antiviral innate immunity,48 was simultaneously involved in two signaling pathways—viral infectious diseases and immune system. IFIT1 (also named p56/ISG56), an innate nucleic acid immune-sensing receptor that can recognize single-stranded viral RNA lacking 2′-O-methylation at the 5′-terminus and thus confers antiviral defense function by disrupting the machinery of host translation initiation,49,50 was also simultaneously related to viral infectious diseases and immune system signaling pathways. By contrast, COL4A1, also known as type IV collagen alpha 1 chain, was simultaneously involved in four of the top five signaling pathways, including viral infectious disease, signal transduction, digestive system, and cancers. This protein is an integral component of basement membranes, which can inhibit the migration, proliferation and tube formation by endothelial cells via binding to α-1/β-1 integrin, and thus becomes a potential therapeutic candidate for targeting tumor angiogenesis.51,52