Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis

Abstract

Objective: Osteosarcoma (OS) is an aggressive, highly metastatic, relatively drug-resistant bone tumor with poor long-term survival rates. The presence and persistence of circulating tumor cells (CTCs) in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases. A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical outcomes. However, traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS, and research on CTC detection in mesenchymal tumors has been hindered for years. Methods: In this study, we developed a CTC test based on hexokinase 2, a metabolic function-associated marker, for the detection and surveillance of OS CTCs, and subsequently explored its clinical value. Twelve patients with OS were enrolled as the training cohort for serial CTC tests. Dynamic CTC counting, in combination with therapy evaluation and post-treatment follow-up, was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival, and the model was further validated with a cohort of 8 patients with OS. Results: Two dynamic CTC number patterns were identified, and the resulting predictive model exhibited 92% consistency with the clinical outcomes. This model suggested that a single CTC test has similar predictive power to serial CTC analysis. In the validation cohort, the single CTC test exhibited 100% and 87.5% consistency with therapy response and disease-free survival, respectively. Conclusions: Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis, and may be clinically valuable for avoiding inefficient therapy and prolonging survival.

Advancements in Circulating Tumor Cell Research: Bridging Biology and Clinical Applications

“…These indicators allow for investigations into novel therapeutic approaches to curb relapse and drug resistance. CTC-based MRD monitoring has also been explored as a valuable tool in post-treatment surveillance, offering insights into the effectiveness of interventions and informing decisions regarding additional therapies [ 79 ]. CTCs can enter a state of dormancy, temporarily evading the immune system and therapeutic interventions [ 80 , 81 ].…”

A novel classification predicts prognosis and drug sensitivity in osteosarcoma based on alterations in gene sets

“…Pre-treatment LDH levels may also help predict chemotherapy response [10,11]. Circulating tumor cells (CTCs): The presence of CTCs in the blood of osteosarcoma patients has been associated with a higher risk of metastasis, and their detection may be useful for monitoring disease progression and response to treatment [12][13][14]. MicroRNAs (miRNAs): These small, non-coding RNA molecules have been implicated in the regulation of various cellular processes, including proliferation, differentiation, and apoptosis.…”

Detection of rare malignant cells in gastric lavage using Hexokinase 2 and single-cell sequencing for early-stage gastric cancer diagnosis

“…Hexokinase (HK) is the initial enzyme of glycolysis that phosphorylates glucose by ATP to glucose 6-phsphates. In previous studies, we have described HK2, an isoform of HK, as a novel biomarker for the detection of rare malignant cells that engage in elevated glycolysis in peripheral blood, urine, and malignant pleural effusion [18][19][20][21] . Similarly, elevated glycolytic activity and increased HK2 expression have also been found in gastric cancer [22][23][24] .…”