Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide, and its noninvasive biomarker-based early detection can significantly increase the chance of potentially curative treatment. Although alpha fetoprotein (AFP), a commonly used cancer biomarker, had been approved by Food and Drug Administration (FDA) for the diagnosis of HCC, the specificity and sensitivity of AFP still fails to well meet the needs for clinical diagnosis, because nearly 30 % HCC patients are AFP negative and AFP is elevated not only in HCC but also in many other diseases.
Recent studies have shown that specific core-fucosylated fraction on AFP has a higher relationship with HCC than AFP. Therefore, to some extent, the analytical methods based on identification of specific glycosylation modification on AFP can allow for precise diagnosis. However, considering only the difference of core-fucose expression still fails to well discriminate HCC patient from the healthy. Besides, although it has been revealed more recently that the expression of terminal sialic acid on the APF glycans is also highly correlated with HCC, due to the difficulty for developing anti-glycans antibodies and inadequate specificity of lectins, there is still no report of the combination of core fucose and sialic acid for precise diagnosis of HCC.
Scheme 1. Illustration of the diagnosis workflow for glycoform-resolved dual-modal ratiometric immunoassay.
For addressing above challenges, Prof. Zhen Liu’s group developed a novel glycoform-resolved dual-modal ratiometric immunoassay, based on the controllable molecular imprinting technology (Angew. Chem. Int. Ed. 2015, 54, 10211-10215; Nat. Protoc. 2017, 12, 964-987; Chem. Sci. 2019, 10, 1831-1835) and plasmonic immunoassay (Angew. Chem. Int. Ed. 2016, 55, 13215–13218; Nat. Protoc. 2021, 16, 3522–3546) the developed previously. By virtue of molecularly imprinted polymers, this novel immunoassay could orthogonally recognize different characteristic fragment of HCC biomarker AFP. Particularly, a “pit one against ten” glycan-imprinted nanomaterial was leveraged for specifically targeting core-fucosylated and/or sialylated glycans. Then, the ratiometric signals from surface enhanced Raman scattering and laser assisted ionization mass spectrometry were used for the precise diagnosis of HCC (Scheme 1).
This research was published online in Angew. Chem. Int. Ed. Prof. Zhen Liu is the corresponding author, Ph.D. candidates Pengfei Li and Jilei Pang are the co-first authors. This work was funded by National Key R&D Program of China (2018YFC0910301) from the Ministry of Science and Technology of China, the Key Grant (21834003) and instrumentation grant (21627810) from the National Natural Science Foundation of China, and the Excellent Research Program of Nanjing University (ZYJH004).
Online link:
https://onlinelibrary.wiley.com/doi/10.1002/anie.202113528