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 appr...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 1.47×10^(12))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.展开更多
Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality rate.However,it has been challenging to establish early detection methods with a single biomarker such as alpha-feto...Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality rate.However,it has been challenging to establish early detection methods with a single biomarker such as alpha-fetoprotein(AFP)because of limited diagnostic sensitivity and specificity.Therefore,developing multiplexed biomarker detection assays is crucially important for early diagnosis.Yet,simultaneous detection methods involving three or more biomarkers have been scarce.Here we suggest employing the serological biomarker panel of glypican-3(GPC3),dickkopf-1(DKK1),and AFP for liver cancer detection.We present a rapid simultaneous detection approach for the biomarker panel labeled with three fluorescent quantum dot nanoprobes(emission wavelengths at 565 nm,605 nm,and 655 nm).As a proof-of-concept,simultaneous fluorescence detection of the biomarker panel was demonstrated using mixed reference samples containing human recombinant GPC3,DKK1,and AFP antigens.Our simultaneous detection approach conferred a linear range of 0.625–2.5 ng·mL^(-1)for the entire biomarker panel,which merits further clinical validation for the simultaneous and accurate determination of the biomarker panel in human serum samples.展开更多
基金This research was supported by grants from National Natural Science Foundation of China （81521091）, the Shanghai Key Laboratory of Hepatobiliary Tumor Biology, and the Ministry of Education （MOE） Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer.
基金supported by the National Natural Science Foundation of China(No.81988101)。
文摘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 1.47×10^(12))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.
基金This work was supported by the National Natural Science Foundation of China(grant number 82073411)。
文摘Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality rate.However,it has been challenging to establish early detection methods with a single biomarker such as alpha-fetoprotein(AFP)because of limited diagnostic sensitivity and specificity.Therefore,developing multiplexed biomarker detection assays is crucially important for early diagnosis.Yet,simultaneous detection methods involving three or more biomarkers have been scarce.Here we suggest employing the serological biomarker panel of glypican-3(GPC3),dickkopf-1(DKK1),and AFP for liver cancer detection.We present a rapid simultaneous detection approach for the biomarker panel labeled with three fluorescent quantum dot nanoprobes(emission wavelengths at 565 nm,605 nm,and 655 nm).As a proof-of-concept,simultaneous fluorescence detection of the biomarker panel was demonstrated using mixed reference samples containing human recombinant GPC3,DKK1,and AFP antigens.Our simultaneous detection approach conferred a linear range of 0.625–2.5 ng·mL^(-1)for the entire biomarker panel,which merits further clinical validation for the simultaneous and accurate determination of the biomarker panel in human serum samples.
