RNA-Seq of Circulating Tumor Cells in Stage II–III Breast Cancer

Lang, Julie E.; Ring, Alexander; Porras, Tania B.; Kaur, Pushpinder; Forte, Victoria; Mineyev, Neal; Tripathy, Debu; Press, Michael F.; Campo, Daniel

doi:10.1245/s10434-018-6540-4

Cited by 53 publications

(46 citation statements)

References 41 publications

(47 reference statements)

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“…Patients with more than 5 CTCs after NCT displayed a worse outcome. Given that CIBOMA/2004-01/ GEICAM/2003-11 trial (ClinicalTrials.gov number, NCT00130533) 13 fail to show a significant survival benefit of adjuvant capecitabine, except in non-basal subgroup 13 , molecular analysis of CTCs, such as genomic profiling 47,48 may able to provide useful information that can help find a patient may benefit from the therapy. As patients with the residual disease with no CTCs displayed better outcomes than patients presenting CTCs after NCT, the benefit of additional adjuvant chemotherapy might be profound in those specific groups.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Gwark

Kim

Kwon

et al. 2020

Sci Rep

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We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80–63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26–155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.

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Section: Discussionmentioning

confidence: 99%

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Gwark

Kim

Kwon

et al. 2020

Sci Rep

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“…The gene expression of single CTCs displays various insights into the modifications that occur in the lifecycle of CTCs [ 22 , 23 ]. Involvement of the immune evasion and survival pathways was shown in the CTCs from colorectal carcinoma [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

Hamid

Gopalan

Matos

et al. 2020

IJMS

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The aim of the present study was to isolate and investigate the genetic heterogeneities in single circulating tumour cells (CTCs) from patients with colorectal carcinoma (CRC). Twenty-eight single CTCs were collected from eight patients with CRC using a negative immunomagnetic enrichment method. After validation with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression in 3 colon cancer cell lines, a panel of 19 genes were used to analyse the single CTCs (n = 28), primary colorectal carcinoma tissues (n = 8) and colon carcinoma cells (n = 6) using real-time qPCR. Genetic heterogeneities were assessed by comparing gene expression profiles of single CTCs from the different patients and in the same patient, respectively. Genetic profiling of the single CTCs showed extensive heterogeneities of the selected genes among the CTCs. Hierarchical clustering analyses exhibited two clusters of CTCs with differentially expressed genes, which highlighted different modifications from the primary carcinomas. Further, the genetic heterogeneities were observed between different patients or in the same patient. Finally, AKT1 expression was significantly (p = 0.0129) higher in single CTCs from CRC of advanced pathological stages (III or IV) CRC than in CTCs from CRC of early stages (I or II). Our findings suggest that single-cell genetic analysis can monitor the genetic heterogeneities and guide the personalised therapeutic targets in clinical sectors.

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“…Genome-wide epigenomic analysis of DNA from liquid biopsy samples might not be possible at the moment, but there are already attempts to probe the methylation status of targeted genes [105] and promoters in CTCs [106]. Single cell RNA sequencing has already been used to investigate CTC transcriptomes in hepatocellular [87] cancer, melanoma [107], pancreatic [108], and breast cancer [109]. Established CTCs protein analysis includes identification of CTCs via antibody staining [96].…”

Section: Current and Emerging Technologiesmentioning

confidence: 99%

The Translational Status of Cancer Liquid Biopsies

Bratulić

Gatto

Nielsen

2019

Regen. Eng. Transl. Med.

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Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient's body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay SummaryPrecision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient's body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research.

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RNA-Seq of Circulating Tumor Cells in Stage II–III Breast Cancer

Abstract: It is feasible to use RNA-seq of CTCs in non-metastatic patients to discover novel tumor biology characteristics.

Cited by 53 publications

References 41 publications

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

The Translational Status of Cancer Liquid Biopsies

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