Clinical Significance of Circulating Tumor Cells (CTCs) and Survivin on Predicting Prognosis in Thyroid Cancer Patients

Weng, Xun; YangYang, undefined; Cai, Yujiao

doi:https://doi.org/10.1155/2022/5188006

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Abstract Introduction Materials and Methods Results Discussion Conclusion Data Availability Ethical Approval Consent Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

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Volume 2022 | Article ID 5188006 | https://doi.org/10.1155/2022/5188006

Clinical Significance of Circulating Tumor Cells (CTCs) and Survivin on Predicting Prognosis in Thyroid Cancer Patients

Xun Weng,¹ YangYang,¹and Yujiao Cai¹

Academic Editor: Fu Wang

Received23 Nov 2021

Accepted21 Dec 2021

Published31 Jan 2022

Abstract

Background. Clinical significance of circulating tumor cell (CTC) count, mesenchymal CTCs (MCTCs), and survivin in patients with thyroid cancer remains unclear. We evaluated the relationship between the expression of different CTC subtypes or survivin and the prognosis in patients with thyroid cancer. Patients and Methods. This study enrolled 164 patients with thyroid cancer who were diagnosed from January 2013 to September 2020 in our hospital. Among these patients, there were 73 cases with papillary thyroid cancer (PTC), 60 cases with follicular thyroid cancer (FTC), 12 medullary thyroid cancers (MTC), 10 poorly differentiated thyroid cancers (PDTC), 9 anaplastic thyroid cancers, and 10 control patients with nonmalignant thyroid nodules based on their histopathological characteristics. Only 5 milliliters (mL) of peripheral blood from the patients with thyroid cancer and control was used to detect the CTC cell number via CanPatrol capture technique before treatments. We also isolated mononuclear cells (MNC) from the peripheral blood and performed quantity reverse transcriptase polymerase chain reaction (qPCR) for survivin gene expression among these patients. Results. The overall positive rates of CTC at diagnosis were 56.1%. The relapse and metastasis rates in PTC and FTC patients with more than 6 CTCs and positive MCTCs were significantly higher than those in the patients with 6 or less than 6 CTCs and MCTCs. It was also found that these patients with >6 CTCs and MCTCs had shorter progression-free survival (PFS). Additionally, the survivin level of the patients with thyroid cancer was strongly relative to differentiation grades of thyroid cancers. Conclusions. The detection of more than six of total CTCs and positive MCTCs in the patients with differentiated thyroid cancer is an excellent biomarker for predicting the prognosis of patients. Survivin also is a good biomarker for thyroid cancer differentiation.

1. Introduction

Worldwide, palpable thyroid nodules can be detected in around 5% of women and 1% of men [1]. Among these patients, only 7-15% patients are malignant [2]. Initial screening of patients with thyroid nodules is currently to utilize ultrasound and fine needle aspiration biopsy (FNAB) [3]. The differentiation between benign and malignant thyroid nodules is still determined by histological examination from the excised thyroid tumor via nodule biopsy or FNAB [4]. Therefore, a few methods, including specific gene detection by polymerase chain reaction (PCR) technique, have been developed for differentiating from benign and malignant thyroid nodules preoperatively [5]. According to the World Health Organization (WHO) on the latest classification of thyroid cancer in 2017 [6], thyroid cancer is mainly classified into papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), Hürthle (oncocytic) cell carcinoma (HCC), medullary thyroid carcinoma (MTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma based on their histopathological characteristics [7, 8]. Among these major classifications, they can further divide into different subclassifications based on their molecular and histopathological feathers [9, 10]. The treatments of the patients with thyroid cancer include surgery, radiation therapy, chemotherapy, hormone therapy, and targeting therapy [11–13]. Surgical resection no doubt is the most effective therapy tool for nonmetastatic thyroid cancer. The prognosis of thyroid cancer is relevant to its histopathological type. Normally, the overall prognosis of PTC and FTC is excellent. Their 5-year overall survival (OS) rate is around 96% [14]. However, HCC, MTC, PDTC, and anaplastic thyroid carcinoma at advanced stages III-IV have very poor prognosis [15]. Therefore, it is urgent to find more reliable and accurate biomarkers for predicting prognosis of patients with thyroid cancer.

Recent studies showed that circulating tumor cells (CTCs) were originally cells from the primary tumor and can be released into bloodstream, which then give rise to tumor metastasis [16, 17]. Different resources have demonstrated that CTC count is a sensitive biomarker to predict tumor progression and helps to make the decision for treatments [18–20]. For example, a study showed that higher CTC level in patients with hepatocellular cancer had strong correlation with early relapse [21]. The other report revealed that epithelial cells from primary tumors can enter into adjacent tissues by the epithelial-mesenchymal transition (EMT) mechanism [22]. CTCs are classified into epithelial type, mesenchymal CTC (MCTC) type, and both mixed types according to their surface markers [23]. So far, CTC evaluation for thyroid cancer mostly has only a few available data, and the results revealed a little correlation with CTC number [5, 23, 24]. Here, as in the previous description, PTC and FTC have good 5-year OS. In contrast, MTC, PDTC, and anaplastic thyroid carcinoma have poor outcomes. Therefore, our study focused on the relationship between CTCs and PTC or FTC patients.

Previous studies showed that thyroid-specific genes, including SLC5A5, TG, TPO, and TSHR, may be excellent candidates for thyroid cancer development [25]. However, some biomarkers like TSHR specificity have been questioned [26]. Therefore, more new biomarkers need to be validated. Recent studies revealed that survivin, a member of the inhibitor of apoptosis (IAP) family [27], is a good biomarker for distinguish benign and malignant thyroid nodules because it is expressed in most cancer cells, not in normal tissues [28–30]. In addition, survivin is also an excellent target for cancer therapy because of its absence in normal cells [31]. In the current study, we detected survivin gene expression and CTC levels of blood circulation from patients with thyroid cancer. This study was to evaluate the clinical significance of CTCs and survivin in the patients with thyroid cancer.

2. Materials and Methods

2.1. Patient Samples

We retrospectively analyzed 164 patients, including PTC, FTC, MTC, PDTC, and anaplastic thyroid carcinoma corresponding to 73, 60, 12, 10, and 9 cases, respectively. These patients were diagnosed based on their histopathological characteristics in our hospital from January 2013 to September 2020. The samples of 10 patients with benign thyroid nodules were the negative control. Diagnosis and staging criteria of all patients were based on the 8^th edition of the American Joint Committee on Cancer (AJCC) staging system for thyroid cancer [32]. All cells were from the peripheral blood of patients at diagnosis. All patients were followed up every 5 months after treatment. For patients with possible recurrence, they were followed up every 2 months. Progression-free survival (PFS) was calculated from the time of the first treatment to relapse or distant metastasis. This study protocol was reviewed and approved by the hospital ethics committee of Xinqiao Hospital, Army Medical University. Written informed consent was obtained from all participated patients.

2.2. Detection of CTCs via CanPatrol and Tricolor RNA-ISH Methods

The characteristic strategies of CTC in patients with thyroid cancer were followed as per the previous description [33]. Briefly, 5 mL peripheral blood was taken from the patients as well as the control at diagnosis. It was spun for 5 minutes at 1500 revolutions per minute (rpm) within four hours after harvesting. The upper plasma phase was discarded, and CTCs were isolated via use of the CanPatrol CTC enrichment technique (SurExam, Guangzhou, China). Alexa Fluor 594-labeled epithelial makers (EpCAM, CK8/18/19), Alexa Fluor 488-conjugated mesenchymal markers (Vimentin and Twist), and nuclear marker (DAPI) were applied to identify CTCs by a tricolor RNA in situ hybridization technique [7]. CTCs were divided into epithelial, mesenchymal, and both mixed types according to the combination of their surface markers with DAPI (shown in Figure 1).

2.3. Survivin Expression by Quantity Reverse Transcription Polymerase Chain Reaction (qPCR)

A peripheral blood mononuclear cell (PBMC) was isolated from 5 mL whole blood of patients before treatment, and 1 mL of TRIzol reagents was added. Total RNA and cDNA syntheses were taken by commercial reagents. Survivin and internal control gene GAPDH TaqMan probe was purchased from Invitrogen. Survivin expression was calculated by ΔΔCt normalized GAPDH.

2.4. Statistical Analysis

The relationship between the CTC-positive rate and the clinic-pathological characteristics was counted via the test. Progression-free survival (PFS) was calculated from the time from initial treatment to local recurrence or distant metastasis by the Kaplan–Meier method and the log-rank test. All results were counted using the GraphPad Prism 9 software. When two-tail values were <0.05, this was considered as statistically significant.

3. Results

3.1. Clinical Characteristics

This study enrolled 164 patients with thyroid cancer at TI-V tumor, node, metastasis (TNM) staging as well as 10 negative controls. The clinic-pathological features of patients are shown in Table 1.Their clinical parameters included age, sex, histology, and TNM staging. The most patients were diagnosed as differentiated thyroid cancer like 73 PTC (44.5%, 71/164) and 60 FTC (36.6%, 60/164). In addition, we also recruited poor differentiated thyroid cancer-like 12 MTC (7.3%, 12/164), 10 PDTC (6.1%, 10/164), and 9 ATC patients (5.5%, 9/164%) for this study. The peripheral blood from these patients was taken for CTC detection and survivin gene expression measurement.

3.2. Identification of CTC Subtypes in Patients with Thyroid Cancer

Samples of 164 thyroid cancer patients and 10 healthy controls were used to enrich CTCs by the CanPatrol technique. CTCs were classified into epithelial, mesenchymal, and both mixed subtypes based on their surface markers with different immunofluorescence dye staining (Figure 1). Our data revealed that the most patients only had a kind of CTC. Only a few epithelial CTCs were detected in benign control. It was found that there were CTCs in 92 out of 164 thyroid cancer patients (56.1%). We compared the CTC-positive rate based on age, gender, pathological subtypes, and TNM staging of the patients with thyroid cancer. It was identified that the positive rate of CTCs was not a positive correlation with age and gender of the patients (). In contrast, CTC-positive rate in different pathological subtypes and TNM staging had dramatic differences. The undifferentiated thyroid cancer, including MTC, PDTC, and ATC patients, and III-IV TNM stages had markedly high CTC-positive rate () (Table 1).

3.3. Comparison of CTC Subtypes in the Patients with Differentiated Thyroid Cancer

To assess the clinical significance of CTC number in different types of patients with thyroid cancer, we compared the total cell number of CTCs and CTC subtypes of major differentiated thyroid cancer PTC and FTC because MTC, PDTC, and ATC are undifferentiated thyroid cancer and have a short overall survival. The results are shown in Figure 2. For total CTCs and mixed CTCs, either PTC or FTC was dramatically higher than the control (Figure 2(a), ). However, there are no significant differences between PTC and FTC (Figures 2(a) and 2(c)). In contrast, for epithelial CTCs (Figure 2(b)) and MCTCs (Figure 2(d)), although both PTC and FTC were dramatically higher than the control (), FTC was also markedly more than PTC (). These results indicated that epithelial CTCs and MCTCs in FTC were higher than PTC.

(a)

(b)

(c)

(d)

3.4. Prognostic Significance of CTC Counts and Subtypes before Treatment

To further evaluate the clinical significance of CTC subtypes, we followed up to 60 months for the patient prognosis. The results are shown in Figure 3 and Table 2. The analyses revealed that PFS in PTC patients (Figure 3(a)) or FTC patients (Figure 3(b)) with were significantly shorter () than that in the patients with by the Kaplan–Meier survival curve analysis. In contrast, PFS of patients with positive MCTCs were also markedly shorter than those with negative MCTCs (, Figures 3(c) and 3(d)). There was a huge difference among different groups (Table 2). in PTC or FTC had a big different hazard ratio and 95% confidence interval (CI) (PTC, HR 8.152, 95% CI 23.12-21.13, ; FTC, HR 5.531, 95% CI 2.33-13.03, ). Similarly, existence of MCTC (PTC, HR 0.131, 95% CI 0.07-0.026, ; FTC, HR 0.136, 95% CI 0.06-0.29, ) had dramatically poorer PFS.

(a)

(b)

(c)

(d)

3.5. Survivin Expression Is Significant Relevant to Thyroid Cancer Differentiation

To investigate the relationship between survivin expression and thyroid cancer differentiation, we measured survivin gene expression by qPCR in patients with thyroid cancer subtype before therapy. The results are shown in Figure 4. With more poor differentiation, survivin had more high expression levels. ATC and PDTC had robust expression compared with the control (). In contrast, PTC or FTC only had some high expression (). Interestingly, survivin expression in ATC also was significant higher than PDTC (). In turn, survivin of PDTC was higher than that of PTC and FTC patients (). These results revealed that survivin is strong relative to the differentiated degree of thyroid cancer.

4. Discussion

Recent studies showed that CTCs were considered to be strongly relevant with cancer development [22, 34]. More data also revealed that CTC count of peripheral blood in cancer patients with advanced staging had an important guideline for predicting prognosis of the patients [18–20]. As for thyroid cancer, a few reports indicated that CTCs of the patients were involved in progress and prognosis [23, 24, 35]. However, CTCs of thyroid cancer patients at early stages have limited availability. Here, our results showed that total CTCs and their subtypes had a significant clinical association with the prediction of differentiated thyroid cancer prognosis.

CTCs in the bloodstream can be frequently characterized into epithelial, mesenchymal, and mixed types according to their surface markers with different immunofluorescence staining. Recent reports indicated that EMT-marker expressions in CTC were relevant to invasion and metastasis in many kinds of cancer like breast cancer, colorectal cancer, nonsmall cell lung cancer, gastric cancer, and prostate cancer [36–39]. For example, Bluemke et al. [40] found that positive CK+ CTCs in renal cancer patients were significantly relevant to their OS [41]. Xu et al. [24] study indicated that if there were more than 5 CTCs in patient’s 5 mL peripheral blood, their prognosis were poor. In the present study, we selected two differentiated thyroid cancer PTC and FTC as our objects because their 5-year OS is long. So we can easily observe the relationships between CTC count and the outcomes. We found that if total CTCs and MCTCs of the PTC or FTC patients were high at diagnosis, they were most likely to have quick tumor progress. We also showed that if the patients had 6 total CTCs or positive MCTCs, their PFS were significantly shorter than the patients with less than 6 total CTCs or negative MCTCs. Similarly, patients with increased MCTC percentage after surgery relapse earlier in hepatocellular cancers [42]. Thus, monitoring of CTC subtypes and changes during treatment of thyroid cancer patients may provide another predictor of recurrence compared with conventional clinical parameters.

In addition to clinical significance of CTC, many studies also explored other biomarkers for the prognosis of thyroid cancer [43–45]. Among these biomarkers, survivin is an interesting gene because it is involved in many kinds of cancers [46, 47]. Survivin is an antiapoptosis protein and is expressed in most tumor cells, not in normal cells [27, 30]. Therefore, surviving is an excellent target for cancer therapy. The Wu et al. [29] study revealed that knockdown survivin may treat papillary thyroid cancer via targeting survivin. This result showed the high survivin promoted thyroid cancer proliferation. Indeed, our data indicated that higher survivin is strongly relevant to poor differentiated thyroid cancer. These data confirmed that survivin also is a good biomarker for the diagnosis and therapy of thyroid cancer.

5. Conclusion

The present study indicated that there was a relationship between CTC subtypes and PFS in patients with thyroid cancer. High CTCs or positive MCTCs were significantly correlated with early recurrence or metastasis. Survivin expression is positively associated with the differentiated degree of thyroid cancer.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Ethical Approval

All human thyroid cancer samples were approved by the ethical committees of Xinqiao Hospital, Army Medical University. This study protocol was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

All patients were given a written informed consent.

Conflicts of Interest

All authors declare that there is no conflict of interest.

Authors’ Contributions

Yujiao Cai conceived and designed the experiments. Xun Weng and Yang Yang performed the experiments and collected data. Xun Weng supported the administration. Xun Weng and Yang Yang handled the study materials and patient information. Yujiao Cai wrote the manuscript. All authors reviewed and approved the manuscript for submission.

Acknowledgments

This study was supported by the National Science Foundation of China (No. 8888888).

References

W. M. G. Tunbridge, D. C. Evered, R. Hall et al., “The spectrum of thyroid disease in a community: the Whickham survey,” Clinical Endocrinology, vol. 7, no. 6, pp. 481–493, 1977.
View at: Publisher Site | Google Scholar
L. Hegedus, “The thyroid nodule,” The New England Journal of Medicine, vol. 351, no. 17, pp. 1764–1771, 2004.
View at: Publisher Site | Google Scholar
B. R. Haugen, “2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed?” Cancer, vol. 123, no. 3, pp. 372–381, 2017.
View at: Google Scholar
Z. al-Hilli, V. Strajina, T. J. McKenzie, G. B. Thompson, D. R. Farley, and M. L. Richards, “The role of lateral neck ultrasound in detecting single or multiple lymph nodes in papillary thyroid cancer,” American Journal of Surgery, vol. 212, no. 6, pp. 1147–1153, 2016.
View at: Publisher Site | Google Scholar
H. G. Jee, B. A. Kim, M. Kim et al., “Expression of SLC5A5 in circulating tumor cells may distinguish follicular thyroid carcinomas from adenomas: implications for blood-based preoperative diagnosis,” Journal of Clinical Medicine, vol. 8, no. 2, 2019.
View at: Google Scholar
R. V. Lloyd, R. Y. Osamura, G. Klöppel, and J. Rosai, WHO classification of tumours of endocrine organs, International Agency for Research on Cancer (IARC). WHO, Lyon, 4th edition, 2017.
P. D. Chin, C. Y. Zhu, D. P. Sajed et al., “Correlation of ThyroSeq results with surgical histopathology in cytologically indeterminate thyroid nodules,” Endocrine Pathology, vol. 31, no. 4, pp. 377–384, 2020.
View at: Publisher Site | Google Scholar
Y. Bai, K. Kakudo, and C. K. Jung, “Updates in the pathologic classification of thyroid neoplasms: a review of the World Health Organization classification,” Endocrinology and Metabolism, vol. 35, no. 4, pp. 696–715, 2020.
View at: Google Scholar
K. Kakudo, A. K. El-Naggar, S. P. Hodak et al., “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in thyroid tumor classification,” Pathology International, vol. 68, no. 6, pp. 327–333, 2018.
View at: Google Scholar
Y. E. Nikiforov, R. R. Seethala, G. Tallini et al., “Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors,” JAMA Oncology, vol. 2, no. 8, pp. 1023–1029, 2016.
View at: Publisher Site | Google Scholar
M. E. Cabanillas, S. Ahmed, and J. R. Wang, “Management of anaplastic and recurrent differentiated thyroid cancer: indications for surgical resection, molecular testing, and systemic therapy,” Neuroimaging Clinics of North America, vol. 31, no. 3, pp. 359–366, 2021.
View at: Google Scholar
Y. Jiang, J. Jin, J. Fan et al., “Urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer,” Biomarkers in Medicine, vol. 15, no. 11, pp. 879–890, 2021.
View at: Google Scholar
F. Nabhan, E. Kander, R. Shen et al., “Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer,” Case Reports in Endocrinology, vol. 2021, Article ID 5521649, 5 pages, 2021.
View at: Publisher Site | Google Scholar
W. Chatchomchuan, Y. Thewjitcharoen, K. Karndumri et al., “Recurrence factors and characteristic trends of papillary thyroid cancer over three decades,” International Journal of Endocrinology, vol. 2021, Article ID 9989757, 7 pages, 2021.
View at: Publisher Site | Google Scholar
J. Barbet, L. Campion, F. Kraeber-Bodere, J. F. Chatal, and Group GTES, “Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma,” The Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 11, pp. 6077–6084, 2005.
View at: Publisher Site | Google Scholar
C. A. Aya-Bonilla, M. Morici, X. Hong et al., “Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells,” British Journal of Cancer, vol. 122, no. 7, pp. 1059–1067, 2020.
View at: Publisher Site | Google Scholar
N. Sawabata, T. Nakamura, T. Kawaguchi et al., “Circulating tumor cells detected only after surgery for non-small cell lung cancer: is it a predictor of recurrence?” Journal of Thoracic Disease, vol. 12, no. 9, pp. 4623–4632, 2020.
View at: Google Scholar
S. J. Cohen, C. J. Punt, N. Iannotti et al., “Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 26, no. 19, pp. 3213–3221, 2008.
View at: Publisher Site | Google Scholar
J. S. de Bono, H. I. Scher, R. B. Montgomery et al., “Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer,” Clinical Cancer Research, vol. 14, no. 19, pp. 6302–6309, 2008.
View at: Google Scholar
D. F. Hayes, M. Cristofanilli, G. T. Budd et al., “Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival,” Clinical Cancer Research, vol. 12, no. 14, pp. 4218–4224, 2006.
View at: Publisher Site | Google Scholar
P. X. Wang, Y. Xu, Y. F. Sun et al., “Detection of circulating tumour cells enables early recurrence prediction in hepatocellular carcinoma patients undergoing liver transplantation,” Liver International, vol. 41, no. 3, pp. 562–573, 2021.
View at: Publisher Site | Google Scholar
D. S. Micalizzi, D. A. Haber, and S. Maheswaran, “Cancer metastasis through the prism of epithelial-to-mesenchymal transition in circulating tumor cells,” Molecular Oncology, vol. 11, no. 7, pp. 770–780, 2017.
View at: Google Scholar
M. Ehlers, S. Allelein, F. Schwarz et al., “Increased numbers of circulating tumor cells in thyroid cancer patients,” Hormone and Metabolic Research, vol. 50, no. 8, pp. 602–608, 2018.
View at: Publisher Site | Google Scholar
J. Y. Xu, B. Handy, C. L. Michaelis et al., “Detection and prognostic significance of circulating tumor cells in patients with metastatic thyroid cancer,” The Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 11, pp. 4461–4467, 2016.
View at: Google Scholar
M. Milas, J. Shin, M. Gupta et al., “Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1758 samples,” Annals of Surgery, vol. 252, no. 4, pp. 643–651, 2010.
View at: Google Scholar
S. Ausavarat, J. Sriprapaporn, B. Satayaban et al., “Circulating thyrotropin receptor messenger ribonucleic acid is not an effective marker in the follow-up of differentiated thyroid carcinoma,” Thyroid Research, vol. 8, p. 11, 2015.
View at: Google Scholar
N. K. Sah, Z. Khan, G. J. Khan, and P. S. Bisen, “Structural, functional and therapeutic biology of survivin,” Cancer Letters, vol. 244, no. 2, pp. 164–171, 2006.
View at: Google Scholar
M. R. Mahmoudian-Sani, A. Alghasi, A. Saeedi-Boroujeni, A. Jalali, M. Jamshidi, and A. Khodadadi, “Survivin as a diagnostic and therapeutic marker for thyroid cancer,” Pathology, Research and Practice, vol. 215, no. 4, pp. 619–625, 2019.
View at: Google Scholar
X. Wu, L. Dai, Z. Zhang, J. Zheng, and J. Zhao, “Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer,” Oncology Letters, vol. 19, no. 1, pp. 61–68, 2020.
View at: Publisher Site | Google Scholar
G. Ambrosini, C. Adida, and D. C. Altieri, “A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma,” Nature Medicine, vol. 3, no. 8, pp. 917–921, 1997.
View at: Google Scholar
M. Pennati, M. Folini, and N. Zaffaroni, “Targeting survivin in cancer therapy,” Expert Opinion on Therapeutic Targets, vol. 12, no. 4, pp. 463–476, 2008.
View at: Google Scholar
M. Tuttle, L. Morris, B. Haugen et al., “Thyroid-differentiated and anaplastic carcinoma (chapter 73),” in AJCC Cancer Staging Manual, vol. 50, no. 8, pp. 602–608, Springer International Publishing, 8th edition, 2017.
View at: Google Scholar
Z. L. Wang, P. Zhang, H. C. Li et al., “Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC,” Cancer Biology & Therapy, vol. 20, no. 4, pp. 505–512, 2019.
View at: Google Scholar
D. H. Moon, D. P. Lindsay, S. Hong, and A. Z. Wang, “Clinical indications for, and the future of, circulating tumor cells,” Advanced Drug Delivery Reviews, vol. 125, pp. 143–150, 2018.
View at: Google Scholar
Z. L. Qiu, W. J. Wei, Z. K. Sun et al., “Circulating tumor cells correlate with clinicopathological features and outcomes in differentiated thyroid cancer,” Cellular Physiology and Biochemistry, vol. 48, no. 2, pp. 718–730, 2018.
View at: Google Scholar
A. Satelli, I. Batth, Z. Brownlee et al., “EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression,” Oncotarget, vol. 8, no. 30, pp. 49329–49337, 2017.
View at: Google Scholar
K. A. Hyun, G. B. Koo, H. Han et al., “Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer,” Oncotarget, vol. 7, no. 17, pp. 24677–24687, 2016.
View at: Google Scholar
T. T. Li, H. Liu, F. P. Li et al., “Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: relevance to therapy response,” World Journal of Gastroenterology, vol. 21, no. 47, pp. 13259–13267, 2015.
View at: Google Scholar
Y. Wang, Y. Liu, L. Zhang et al., “Vimentin expression in circulating tumor cells (CTCs) associated with liver metastases predicts poor progression-free survival in patients with advanced lung cancer,” Journal of Cancer Research and Clinical Oncology, vol. 145, no. 12, pp. 2911–2920, 2019.
View at: Google Scholar
K. Bluemke, U. Bilkenroth, A. Meye et al., “Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis,” Cancer Epidemiology, Biomarkers & Prevention, vol. 18, no. 8, pp. 2190–2194, 2009.
View at: Google Scholar
C. Garrido-Navas, D. de Miguel-Perez, J. Exposito-Hernandez et al., “Cooperative and escaping mechanisms between circulating tumor cells and blood constituents,” Cell, vol. 8, no. 11, p. 1382, 2019.
View at: Publisher Site | Google Scholar
L. N. Qi, B. D. Xiang, F. X. Wu et al., “Circulating tumor cells undergoing EMT provide a metric for diagnosis and prognosis of patients with hepatocellular carcinoma,” Cancer Research, vol. 78, no. 16, pp. 4731–4744, 2018.
View at: Google Scholar
A. B. Cefalù, A. Giammanco, D. Noto et al., “Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome,” Endocrine, vol. 71, no. 2, pp. 344–350, 2021.
View at: Publisher Site | Google Scholar
E. V. Proskurnina, M. V. Fedorova, M. M. Sozarukova, A. E. Mitichkin, I. V. Panteleev, and E. V. Svetlov, “Microsomal reductase activity in patients with thyroid neoplasms,” Endocrine, vol. 72, 2020.
View at: Google Scholar
X. Zou, F. Gao, Z. Y. Wang et al., “A three-microRNA panel in serum as novel biomarker for papillary thyroid carcinoma diagnosis,” Chinese Medical Journal, vol. 133, no. 21, pp. 2543–2551, 2020.
View at: Publisher Site | Google Scholar
P. Yu, A. X. Li, X. S. Chen et al., “PKM2-c-Myc-survivin cascade regulates the cell proliferation, migration, and tamoxifen resistance in breast cancer,” Frontiers in Pharmacology, vol. 11, p. 550469, 2020.
View at: Google Scholar
R. A. Syahrani, E. Yunita, and S. I. Wanandi, “Suppression of rotenone-treated human breast cancer stem cell survival using survivin inhibitor YM155 is associated to oxidative stress modulation,” Asian Pacific Journal of Cancer Prevention, vol. 21, no. 9, pp. 2631–2637, 2020.
View at: Google Scholar

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