Covalent Chemistry‐Mediated Multimarker Purification of Circulating Tumor Cells Enables Noninvasive Detection of Molecular Signatures of Hepatocellular Carcinoma

Transcriptomic profiling of tumor tissues introduces a large database, which has led to improvements in the ability of cancer diagnosis, treatment, and prevention. However, performing tumor transcriptomic profiling in the clinical setting is very challenging since the procurement of tumor tissues is inherently limited by invasive sampling procedures. Here, the feasibility of purifying hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from clinical patient samples is demonstrated with improved molecular integrity using Click Chips in conjunction with a multimarker antibody cocktail. The purified CTCs are then subjected to messenger RNA profiling by NanoString nCounter platform, targeting 64 HCC‐specific genes, which are generated from an integrated data analysis framework with eight tissue‐based prognostic gene signatures from seven publicly available HCC transcriptomic studies. After bioinformatics analysis and comparison, the HCC CTC‐derived gene signatures show high concordance with HCC tissue‐derived gene signatures from the Cancer Genome Atlas database, suggesting that HCC CTCs purified by Click Chips can enable the translation of HCC tissue molecular profiling into a noninvasive setting. Covalent chemistry‐mediated multimarker purification of hepatocellular carcinoma circulating tumor cells (HCC CTCs) is developed to realize noninvasive detection of molecular signatures of HCC. The purification system enables improved purity and molecular integrity of the purified HCC CTCs for conducting transcriptomic profiling of a strictly selected HCC‐specific gene panel.