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Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
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Single-Cell Genomics-Based Molecular Algorithm for Early Cancer Detection.

Zhuo Wang1, Yuyang Zhao2, Xiaohan Shen1

  • 1Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer (SMHC), Minhang Hospital and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Analytical Chemistry
|January 25, 2022
PubMed
Summary
This summary is machine-generated.

A new molecular algorithm, scCancerDx, confirms malignancy in suspicious cells from body fluids for definitive cancer diagnosis. This method, validated with hexokinase 2 (HK2), aids early bladder cancer detection using urine samples.

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Area of Science:

  • Oncology
  • Genomics
  • Biotechnology

Background:

  • Liquid biopsy offers noninvasive detection of cancer markers but lacks definitive diagnostic capability.
  • Single-cell genomics is challenged by technical noise and inter-cell variability for confirming malignancy without reference tumor tissue.
  • Accurate diagnosis of suspicious cells in body fluids remains a significant hurdle in early cancer detection.

Purpose of the Study:

  • To develop a molecular algorithm, scCancerDx, for confirming cell malignancy using single-cell copy number alteration profiles.
  • To validate hexokinase 2 (HK2) as a marker for disseminated tumor cells.
  • To investigate the early detection of bladder cancer (BC) using scCancerDx and HK2 in urine.

Main Methods:

  • Developed and trained the scCancerDx algorithm using normal cells and cancer cell lines.
  • Validated scCancerDx with single tumor cells from clinical samples.
  • Identified and validated hexokinase 2 (HK2) as a metabolic marker for disseminated tumor cells across various cancer types.
  • Assessed the preclinical efficacy of an HK2-based test combined with scCancerDx for early bladder cancer detection in urine.

Main Results:

  • The scCancerDx algorithm successfully confirms cell malignancy from single-cell copy number alternation profiles.
  • Hexokinase 2 (HK2) was validated as an efficient marker for identifying disseminated tumor cells in various body fluids.
  • The combined scCancerDx and HK2 approach showed potential for early bladder cancer detection by identifying high-glycolytic tumor cells in urine.

Conclusions:

  • scCancerDx provides a definitive cancer diagnosis by confirming cell malignancy from body fluid samples.
  • HK2 is a promising biomarker for detecting disseminated tumor cells, aiding in early cancer identification.
  • The integration of scCancerDx and HK2 holds significant promise for noninvasive early detection of cancers like bladder cancer, improving patient outcomes.