3.3 Critical lipids screening through Venn Diagram and Pathway analysis
We identified 44 lipids differentially expressed both in the mild and severe ICP group compared with the control group (Fig 3A). Detailed information regarding the 44 differential lipids was shown in Table 2. To screen critical lipids that are associated with ICP, we combined the previously published ICP plasma lipidomics data for further analysis23. In the previously reported data, Sun et al revealed differentially expressed plasma lipids in ICP patients, and we identified three differential lipids co-expressed both in ICP placenta and ICP plasma (Fig 3A). These three lipids are SM (d42:1), SM (d18:1/24:1) and PC (17:0/18:2), and their expression level in the ICP placenta is significantly altered (Fig 3C). Based on the identified 44 differential lipids, we conducted a pathway analysis to reveal possible metabolic pathways involved in ICP onset. The results of the pathway analysis show that the significantly altered lipids were enriched in autophagy regulation, glycerophospholipid metabolism and GPI-anchor biosynthesis (Fig 3B). It was reported autophagy is closely related to ICP pathogenesis14, 25, 26, we further analyzed the individual autophagy pathways and found 5 PE lipids are closely in correlation with autophagy (Fig S1), including PE (16:0/18:1), PE (16:0/20:2), PE (18:1/20:3), PE (18:1/20:4), exhibited increased level in ICP placenta, while PE (18:0/22:4) exhibited decreased expression level (Fig 3C), indicate these lipids may play a pivotal role in the occurrence and development of ICP.