The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells

Gazzaniga, Paola; Raimondi, Cristina; Nicolazzo, Chiara; Carletti, Raffaella; Gioia, Cira Di; Gradilone, Angela; Cortesi, Enrico

doi:10.1586/14737159.2015.1045491

Cited by 20 publications

(17 citation statements)

References 41 publications

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“…These identified DEGs were probably derived from the circulating tumor cells (CTCs), which shed into the vasculature from a primary tumor and circulated through the bloodstream [15]. Previous studies demonstrated that CTCs contained a variety of mRNAs that played vital roles for subsequent growth of additional tumors in vital distant organs, triggering a mechanism for the vast majority of cancer-related deaths [16–18], and their levels gradually increased with the increase in tumor staging [19–20]. It indicated that the increase number of DEGs with the progression of hepatic carcinoma might be caused by the growth of CTCs, and the number of DEGs might be able to be used for supervising the progression of hepatic carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq

Shen

et al. 2017

Oncotarget

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Tumor metastasis is a multistep process involving a number of genetic alterations so that the genetic diagnosis is got increasingly attentions today. The aim of this study was to use RNA-seq to screen the effective differential expression genes in the peripheral blood mononuclear cells for the hepatic carcinoma with metastasis. The results showed that hepatic carcinoma samples gathered according to different metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in inflammation mediated by chemokine and cytokine signaling pathway (P00031) in the hepatic carcinoma samples with metastasis, and subsequently confirmed by quantitative real-time polymerase chain reaction. In conclusions, CCL3, CCL3L1, JUN, IL8, and IL1B have the potential to be considered as candidates for future molecular diagnosis of the hepatic carcinoma with metastasis. This work may provide us with new visions into the metastasis process and potential efficient clinical diagnosis in the future.

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Section: Discussionmentioning

confidence: 99%

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq

Shen

et al. 2017

Oncotarget

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“…These techniques generally rely on cell surface antigen expression for capturing CTCs or cell size to enrichment of CTCs by filtration techniques. CTC isolation methods and instruments were elaborately reported recently (8)(9)(10)(11). In our study, we used commercially available immunomagnetic beads coated with the monoclonal antibody Ber-EP4 (12), which recognizes specific epitopes of the extracellular domain of the EpCAM molecule.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

Liu¹,

Ling²,

Qi³

et al. 2017

Molecular and Clinical Oncology

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Abstract. The identification of circulating tumor cells (CTCs) may provide important prognostic information in several types of solid tumors, including gastric cancer. The aim of this study was to investigate whether CTC count may be used to predict survival in patients with advanced gastric cancer treated with chemotherapy. The CELLection™ Epithelial Enrich kit was used to isolate and purify CTCs from samples of peripheral blood. Immunofluorescent staining was used for CTC counting. High CTC counts were associated with poor tumor differentiation and high serum CEA levels (P=0.021 and 0.005, respectively). After 3 months, 16 patients with decreasing CTC counts after the first cycle of chemotherapy obtained complete response, partial response or stable disease, while 13 patients with increasing CTC counts developed progressive disease. The patients with decreasing CTC counts also exhibited longer progression-free survival (PFS) (P≤0.001) and overall survival (OS) (P= 0.002) compared with those with increasing CTC counts. Among all 59 patients, those with a CTC count of ≤2 cells̸5 ml blood exhibited longer PFS (P≤0.001) and OS (P≤0.001) compared with those with a CTC count of >2 cells̸5 ml blood. The multivariate analysis suggested that an increase of the CTC count after the first cycle of chemotherapy was only an independent prognostic marker of poor PFS (P=0.019). However, a baseline CTC count of >2 cells̸5 ml blood was an independent poor prognostic marker for PFS (P= 0.008) and OS (P= 0.001) in all 59 patients. Our study suggested that patients with a low baseline CTC count or decrease of the CTC count after the first cycle of chemotherapy may benefit significantly from palliative chemotherapy. In conclusion, CTC count may be a good chemotherapy monitoring marker and an ideal prognostic marker for patients receiving palliative chemotherapy.

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“…Nevertheless, up to 40% of patients have CEA levels within normal range, thereby limiting its relevance for the entire patient population. As a result, liquid biopsy modalities, mainly CTCs and circulating tumor DNA (ctDNA) are being explored in a variety of clinical settings in CRC [25], [26]. In this respect, the relative advantages of the ISET system, which captures a more diverse cell population and allows for the enumeration, genotypic and phenotypic characterization of CTCs, led us to explore its utility.…”

Section: Discussionmentioning

confidence: 99%

Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer

Matikas

Voutsina

Lagoudaki

et al. 2017

Translational Oncology

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INTRODUCTION: The presence of KRAS mutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RAS wild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRAS mutated clones. In this feasibility study, we aimed to detect KRAS exon 2 mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system. METHODS: CTC isolation using the ISET system was performed from prospectively collected blood samples obtained from patients with RAS and BRAF WT mCRC prior to first-line therapy initiation, at first imaging assessment and on disease progression. CTCs were enumerated using hematoxylin & eosin and CD45 double stain on a single membrane spot. DNA was extracted from 5 spots and KRAS exon 2 mutations were detected using a custom quantitative Polymerase Chain Reaction (qPCR) assay. RESULTS: Fifteen patients were enrolled and 28 blood samples were analyzed. In 9 (60%) patients, at least one sample was positive for the presence of a KRAS exon 2 mutation. In 11 out of 28 samples (39.2%) with detectable CTCs a KRAS mutation was detected; the corresponding percentages for baseline and on progression samples were 27% and 37.5%, respectively. The most commonly detected mutations were G13D and G12C (n = 3). The presence of KRAS mutated CTCs at baseline was not prognostic for either PFS (P = .950) or OS (P = .383). CTC kinetics did not follow tumor response patterns. CONCLUSION: The results demonstrate that using a qPCR-based assay, KRAS exon 2 mutations could be detected in CTCs captured by the ISET system from patients with RAS WT primary tumors. However, the clinical relevance of these CTCs remains to be determined in future studies.

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The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells

Cited by 20 publications

References 41 publications

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq

Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer

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