Detection and Prognostic Significance of Circulating Tumor Cells in Patients With Metastatic Thyroid Cancer

Xu, Jian; Handy, Beverly Carol; Michaelis, Christina L.; Waguespack, Steven G.; Hu, Mimi I.; Busaidy, Naifa L.; Jimenez, Camilo; Cabanillas, Maria E.; Fritsche, Herbert A.; Cote, Gilbert J.; Sherman, Steven I.

doi:10.1210/jc.2016-2567

Cited by 38 publications

(39 citation statements)

References 16 publications

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“…Although EpCAM expression has reportedly been found in DTC specimens, those CTCs have not been successfully isolated by means of anti-EpCAM Ab. The reason may be that down-regulated membrane expression and up-regulated nuclear accumulation of EpCAM are associated with EMT during DTC progression and metastasis [13]. This is consistent with the observation of Xu et al using CellSearch [13].…”

Section: Discussionsupporting

confidence: 80%

“…The CellSearch system is the most widely used assay for CTCs, and depends on expression of CTC-surface epithelial cell adhesion molecule (EpCAM) [12]. However, the CellSearch system has a low detection rate for DTC CTCs, probably due to their low EpCAM expression during epithelial-mesenchymal transition (EMT) [13]. Negative enrichment (NE) combined with immunofluorescence and in situ chromosomal hybridization (NE-iFISH) is reportedly effective in detecting CTCs from gastric or pancreatic cancers [14] [15], but its use in detecting CTCs from metastatic DTC has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Qiu¹,

Wei²,

Sun³

et al. 2018

Cell Physiol Biochem

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Background/Aims: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence–in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). Methods: In this prospective study, we enrolled 72 patients with DTC before they underwent ¹³¹I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE–iFISH technique. CTC was defined by the aneuploidy. Results: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM⁺) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM^-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM⁺ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to ¹³¹I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM⁺ DTC (P< 0.001). Conclusion: We found CTCs ≥ 5 to be a potential predictive index for DM⁺ DTC; and CTCs ≥7 as a possible indicator of poor response to ¹³¹I treatment and worse prognosis in DM⁺ DTC.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Qiu¹,

Wei²,

Sun³

et al. 2018

Cell Physiol Biochem

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“…The local recurrence and distant metastasis are the main reasons for PTC induced death. Accumulating studies have highlighted the fact that circulating tumor cells are responsible for the metastasis of cancers, including PTC (Xu et al, ). Given that the superior bioavailability and antitumor efficacy of DATS, we speculate that DATS is capable of killing both local thyroid cancer cells and circulating tumor cells in PTC patients by releasing H 2 S.…”

Section: Discussionmentioning

confidence: 99%

Diallyl trisulfide, a H₂S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H₂S and cystathionine‐gamma‐lyase

Pan

Cheng

et al. 2020

Phytotherapy Research

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Diallyl trisulfide (DATS), derived from garlic, is a well‐known hydrogen sulfide (H2S) donor. H2S has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The present study demonstrated that DATS along with other two H2S donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC‐1 cells growth. DATS treatment triggered a rapid H2S generation within 5 min in KTC‐1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating H2S contributed to the apoptosis‐inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma‐lyase (CTH), one of H2S‐producing enzymes, which was responsible for endogenous H2S generation. After DATS treatment, H2S quickly permeated cell membranes and activated NF‐κΒ/p65 signaling pathway in KTC‐1 cells. Nuclear translocated NF‐κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous H2S elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous H2S. This positive feedback sustained excess H2S production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel H2S‐based antitumor agents.

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“…Regarding thyroid malignancies, only limited data are available: overexpression of the epithelial cell adhesion molecule (EpCAM) on tumor tissue was found in DTC and poorly DTC in contrast to anaplastic thyroid carcinomas [9] indicating the usability of EpCAM staining to identify CTCs in DTCs. In line with this, Xu et al recently described EpCAM-positive CTCs in TC: using EpCAM expression for enrichment (Cell-Search System, Veridex LLC, USA), the presence of ≥ 5 CTCs/8 ml peripheral blood in patients with metastatic MTC has been described to be associated with worse overall survival [10].…”

Section: Introductionmentioning

confidence: 86%

Increased Numbers of Circulating Tumor Cells in Thyroid Cancer Patients

et al. 2018

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Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3×10 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels<0.3 ng/ml (no evidence of tumor recurrence) revealed a significantly higher amount of CTCs, also associated to their former tumor stage. Regarding the tumor-free papillary TC (PTC) patients the number of CTCs additionally correlated to the time point of radioiodine (RI) therapy: PTC patients with RI therapies>8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy<8 years ago. We found a clear correlation between the number of CTCs and the tumor stage. Importantly, PTC patients who are in remission may still have increased numbers of CTCs. Follow-up analyses in these patients will reveal whether these data will have a clinical impact.

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Detection and Prognostic Significance of Circulating Tumor Cells in Patients With Metastatic Thyroid Cancer

Abstract: The presence of more than or equal to 5 CTCs in patients with metMTC is associated with worse OS. Larger cohorts are required to validate the prognostic value of CTC enumeration.

Cited by 38 publications

References 16 publications

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Diallyl trisulfide, a H₂S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H₂S and cystathionine‐gamma‐lyase

Increased Numbers of Circulating Tumor Cells in Thyroid Cancer Patients

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Detection and Prognostic Significance of Circulating Tumor Cells in Patients With Metastatic Thyroid Cancer

Abstract: The presence of more than or equal to 5 CTCs in patients with metMTC is associated with worse OS. Larger cohorts are required to validate the prognostic value of CTC enumeration.

Cited by 38 publications

References 16 publications

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Diallyl trisulfide, a H2S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H2S and cystathionine‐gamma‐lyase

Increased Numbers of Circulating Tumor Cells in Thyroid Cancer Patients

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Diallyl trisulfide, a H₂S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H₂S and cystathionine‐gamma‐lyase