Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progression. Sialylation is essential for early embryonic development and the deletion of UDP-GlcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.
Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl](-) form of LPC(16:0) in its tandem mass spectrum.
Disease-specific immune response-related protein complexes in the bloodstream are associated with disease status. We used proteomic technologies to screen novel circulating immunoinflammation-related protein complexes (IIRPCs) and to evaluate their diagnostic accuracy. The discovery study included 96 gastric cancer patients and 83 healthy controls and was designed to isolate and identify the IIRPCs. Then an independent validation study including 1366 patients with lung, colorectal, pancreatic, gastric, or thyroid cancer, 141 patients with other types of cancer, 376 patients with benign lung, colorectal, pancreatic, gastric, or thyroid diseases, and 3707 healthy controls was performed. We observed seven major patterns of the IIRPCs and confirmed the IIRPCs as personalized biomarkers of cancers. The levels of the IIRPCs were significantly increased in cancer patients compared with controls and benign patients (p < 0.0001). Each of the IIRPCs (a2 to a4, a6, a7, and b3 to b5) shows excellent discriminating power for lung, colorectal, pancreatic, and gastric cancer, with the areas under the receiver operating characteristic curves (AUCs) from 0.95 to 0.99 (95% CIs 0.91-1.00), and for thyroid cancer, with the AUCs from 0.87 to 0.96 (95% CIs 0.80-0.98). The IIRPCs can be used as a novel type of broad-spectrum and supramolecular biomarker for personalized cancer diagnosis.
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