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Detection of Circulating Tumor Cells Using Membrane-Based SERS Platform: A New Diagnostic Approach for 'Liquid Biopsy'.

ABSTRACT: The detection and monitoring of circulating tumor cells (CTCs) in blood is an important strategy for early cancer evidence, analysis, monitoring of therapeutic response, and optimization of cancer therapy treatments. In this work, tailor-made membranes (MBSP) for surface-enhanced Raman spectroscopy (SERS)-based analysis, which permitted the separation and enrichment of CTCs from blood samples, were developed. A thin layer of SERS-active metals deposited on polymer mat enhanced the Raman signals of CTCs and provided further insight into CTCs molecular and biochemical composition. The SERS spectra of all studied cells-prostate cancer (PC3), cervical carcinoma (HeLa), and leucocytes as an example of healthy (normal) cell-revealed significant differences in both the band positions and/or their relative intensities. The multivariate statistical technique based on principal component analysis (PCA) was applied to identify the most significant differences (marker bands) in SERS data among the analyzed cells and to perform quantitative analysis of SERS data. Based on a developed PCA algorithm, the studied cell types were classified with an accuracy of 95% in 2D PCA to 98% in 3D PCA. These results clearly indicate the diagnostic efficiency for the discrimination between cancer and normal cells. In our approach, we exploited the one-step technology that exceeds most of the multi-stage CTCs analysis methods used and enables simultaneous filtration, enrichment, and identification of the tumor cells from blood specimens.

SUBMITTER: Kaminska A

PROVIDER: S-EPMC6473992 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Tumor-proximal liquid biopsy to improve diagnostic and prognostic performances of circulating tumor cells.

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2019-07-24 | GSE117623 | GEO

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Project description:In the era of personalized medicine, molecular profiling of patient tumors has become the standard practice, especially for patients with advanced disease. Activating point mutations of the KRAS proto-oncogene are clinically relevant for many types of cancer, including colorectal cancer (CRC). While several approaches have been developed for tumor genotyping, liquid biopsy has been gaining much attention in the clinical setting. Analysis of circulating tumor DNA for genetic alterations has been challenging, and many methodologies with both advantages and disadvantages have been developed. We here developed a gold nanoparticle-based rapid strip test that has been applied for the first time for the multiplex detection of KRAS mutations in circulating tumor DNA (ctDNA) of CRC patients. The method involved ctDNA isolation, PCR-amplification of the KRAS gene, multiplex primer extension (PEXT) reaction, and detection with a multiplex strip test. We have optimized the efficiency and specificity of the multiplex strip test in synthetic DNA targets, in colorectal cancer cell lines, in tissue samples, and in blood-derived ctDNA from patients with advanced colorectal cancer. The proposed strip test achieved rapid and easy multiplex detection (normal allele and three major single-point mutations) of the clinically relevant KRAS mutations in ctDNA in blood samples of CRC patients with high specificity and repeatability. This multiplex strip test represents a minimally invasive, rapid, low-cost, and promising diagnostic tool for the detection of clinically relevant mutations in cancer patients.

| S-EPMC8869478 | biostudies-literature

Circulating Tumor Cell Detection by Liquid Biopsy during Early-Stage Endometrial Cancer Surgery: A Pilot Study.

Project description:The recurrence of non-metastatic endometrial carcinoma (EC) (6 to 21%) might be due to disseminated tumor cells. This feasibility study investigated whether circulating tumor cells (CTCs) were detectable in blood samples from the peripheral and ovarian veins of 10 patients undergoing laparoscopic resection of stage I-II EC between July 2019 and September 2021. CTCs were detected using the CellSearch® system (i) preoperatively (T0) in peripheral blood, (ii) after ovary suspensory ligament pediculation in ovarian vein blood (T1), and (iii) before colpotomy in peripheral blood (T2). CTCs were detected only in ovarian vein samples in 8/10 patients. The CTC median number did not differ with patient age (37 (min-max: 0-91) in <70-year-old vs. 11 (0-65) in ≥70 year-old women, p = 0.59), tumor grade (15 (0-72) for grade 1 vs. 15 (0-91) for grade 2, p = 0.97), FIGO stage (72 (27-91) vs. 2 (0-65) vs. 3 (0-6]) for stage IA, B, and II, respectively; p = 0.08), and tumor size (40 (2-72) for size < 30 mm vs. 4 (0-91) for size ≥ 30 mm, p = 0.39). Estrogen receptor-positive CTCs and CTC clusters were identified. The prognostic and therapeutic values of CTCs released during EC surgery need to be determined.

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Liquid Biopsy in Metastatic Breast Cancer: Current Role of Circulating Tumor Cells and Circulating Tumor DNA.

Project description:BackgroundIn metastatic breast cancer (MBC), blood-based diagnostics have become a major focus of oncological research in the last 2 decades. Detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) has the potential to improve prognosis assessment and complement standard therapy monitoring tools.SummaryTo date, several large analyses have confirmed high CTC counts as an independent prognostic factor. Persistently high CTC numbers during systemic treatment are associated with early progression, but it remains to be clarified which therapeutic options should be offered to such patients since the SWOG 0500 trial failed to show benefit from early switch to another chemotherapy regimen in patients with CTC persistence. In comparison, evidence on the prognostic value of ctDNA is still limited. Most importantly, liquid biopsy-guided treatment interventions have been investigated in several trials. In patients with hormone receptor-positive and HER2-negative MBC, CTC-driven therapy choices resulted in similar PFS to physician's choice treatment. Recently, the DETECT III trial has shown that patients with HER2-negative MBC and HER2-positive CTCs may benefit from targeted anti-HER2 treatment with lapatinib. ctDNA-driven therapy selection has already been approved in clinical routine: alpelisib is the first targeted treatment indicated on the basis of a ctDNA test. Key Messages: CTCs and ctDNA predict clinical outcome and have a potential to improve therapy choices in MBC.

| S-EPMC8985043 | biostudies-literature

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