A clinically feasible circulating tumor cell sorting system for monitoring the progression of advanced hepatocellular carcinoma

Abstract

Background Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. Results The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. Conclusions The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.

Receptor-interacting protein kinase 2 is associated with tumor immune infiltration, immunotherapy-related biomarkers, and affects gastric cancer cells growth in vivo

“…Previous research has demonstrated that TMB is indicative of immunotherapy efficacy, with higher TMB values associated with greater tumor inhibition and clinical benefits resulting from immunotherapy. Conversely, lower TMB values are associated with diminished clinical benefits derived from immunotherapy 47 . The study demonstrated a positive correlation between the expression of RIPK2 and the TMB and MSI in different types of tumors, including stomach adenocarcinoma (STAD).…”

Comprehensive Genomic Profiling Identifies FAT1 as a Negative Regulator of EMT, CTCs, and Metastasis of Hepatocellular Carcinoma

“…20 On the other hand, knockdown of FAT1 also led to rapid loss of basal cell polarity as well as adhesion and tight junctions, thus promoting tumor progression. 21 In this study, we captured CTCs from HCC patients using our modified CTC capture method, 22 and extracted HCC tissues and CTC DNAs for next generation sequencing (NGS). We then combined the sequencing data from tissue and CTC to screen the FAT1 gene of interest, and cultured the HCC cell lines in a simulated blood environment and collected the treated tumor cells with magnetic beads.…”

Dual-aptamer-based colorimetric assay for the accurate identification of circulating tumor cells via Fe3O4@Pt NP nanozymes and G-quadruplex/hemin for signal amplification

“…3 Studies have demonstrated that CTCs can act as a tumor marker for the early diagnosis of cancer, monitoring of treatment effectiveness and prognosis assessment. 4–7 In addition, CTC analysis is noninvasive, and in such a scenario, more acceptable by patients than traditional tissue biopsy. 8 However, CTCs are extremely rare in the bloodstream of patients (one to hundreds per mL).…”