A Time-Resolved Proteotranscriptomic Atlas of the Human Placenta Reveals Pan-Cancer Immunomodulators

The placenta separating embryo and mother plays a major role in evading rejection by the maternal immune system. Tumor cells utilize similar strategies to coexist in an immunologically hostile environment. Exploration of placental development help us increase understanding of the immune aspects of pan-cancer. However, a system-wide placental development analysis of the underlying immune changes remains elusive. Here, we constructed the comprehensive time-resolved atlas of human placental tissues and presented an integrated proteotranscriptomic analysis. The liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to quantify proteins extracted from 15 immature placenta and 6 mature placenta tissues. And the quantitative transcriptome atlas was depicted based on RNA-seq. We found that the amount and abundance of proteins detected in immature placenta were more than mature placenta. Moreover, protein abundance was incompletely predicted by transcriptome, presenting functional differences. In addition, dynamically expressed proteins ubiquitously involved in human placenta development and were significantly related to immune pathways. Based on the striking similarities between placental cells and cancer cells, co-differentially expressed genes (co-DEGs) from placenta time-resolved multi-omics data were identified to dissect cancer-related genes and cluster cancer types with similar tissue origins. As results, we identified key immunomodulators in the placenta, whose expression tend to dysregulated in pan-cancer and are strongly correlated with pan-cancer immune scores as well as clinical outcomes. Overall, our study provides a resource to view the altered immune regulation driven by the placenta and demonstrates the benefit of placental analysis in cancer tumorigenesis. Funding Statement: This work was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2M-1-001), National Key R&D Program of China (2017YFC0906603), the Open Project Program of the State Key Laboratory of Proteomics (SKLP-O201705), the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2M-3-005), the National Natural Science Foundation of China (31571331, 61873075, 31871338), Natural Science Foundation for Distinguished Young Scholars of Heilongjiang Province (JQ2019C004). Declaration of Interests: The authors declare no competing interests. Ethical Approval Statement: All donors signed informed consent forms. The use of human tissue samples and experimental procedures for this study were reviewed and approved by the Ethics Committee of the Cancer Institute and Hospital, Chinese Academy of Medical Sciences.