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An intelligent serological SERS test toward early-stage hepatocellular carcinoma diagnosis through ultrasensitive nanobiosensing

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Abstract

Early or very early detection of hepatocellular carcinoma (HCC) is an effective means to resolve the low cure rates, but there currently lacks a method that fulfills clinical requirements. One of the most prospective approaches to detecting early-stage HCC is directly testing a compendium of disease-relevant biomolecules contained within human serum through surface-enhanced Raman scattering (SERS) nanobiosensing and recognizing the biomolecular patterns. We report a novel Si-based bimetallic nanoensembles-functionalized SERS substrate (its analytical enhancement factor reaches 1.47 × 1012) and introduce an ultrasensitive nanobiosensing for capturing the subtle characteristic changes in SERS spectra caused by HCC, hepatitis B, or cirrhosis. Toward early diagnosis, we created an intelligent serological test with this nanobiosensing and the deep learning algorithm to gain key biomolecular phenotypes of early-stage HCC. Using clinical samples from four target populations (normal, HCC, cirrhosis, and hepatitis B), the proof-of-principle result indicates that the test yielded a predictive accuracy of 98.75% on a held-out dataset (randomly drew 4 out of 28 samples per population). On the same held-out dataset, the sensitivity and specificity of the test were both 100% for distinguishing HCC. Such a new-concept liquid biopsy could provide an opportunity for early diagnosis of HCC.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81988101). The authors would like to thank Qing Shao and Yin Yang for their hard work in preparing the SERS substrate.

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  1. Ningtao Cheng and Bin Lou contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Ningtao Cheng & Hongyang Wang

  2. Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Bin Lou

  3. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China

    Hongyang Wang

  4. National Center for Liver Cancer, Shanghai, 201805, China

    Hongyang Wang

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  1. Ningtao Cheng
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  2. Bin Lou
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Correspondence to Hongyang Wang.

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Cheng, N., Lou, B. & Wang, H. An intelligent serological SERS test toward early-stage hepatocellular carcinoma diagnosis through ultrasensitive nanobiosensing. Nano Res. 15, 5331–5339 (2022). https://doi.org/10.1007/s12274-022-4114-z

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  • DOI: https://doi.org/10.1007/s12274-022-4114-z

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