Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Zhang, Xuehui; Li, Hui; Yu, Xijie; Li, Shanxin; Lei, Zhen; Li, Chang; Zhang, Qun; Han, Qing; Li, Yuan; Zhang, Kun; Wang, Yuxiang; Liu, Congrong; Mao, Youdong; Wang, Xi; Irwin, David M.; Guo, Hongyan; Niu, Gang; H, Tan

doi:10.1159/000492521

Cited by 69 publications

(74 citation statements)

References 43 publications

(52 reference statements)

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“…Ovarian cancer (OC) is s the seventh most common cancer and a type of gynaecological malignancies, with high mortality in females [1][2][3]. The majority of ovarian cancers (nearly 90%) are originated from epithelial tissues [4,5]. Despite ongoing efforts to find effective treatment methods for OC, the overall survival rate remains less than 30%, which was mainly caused by the difficulty for early diagnosis, and often results in a poor prognosis [6,7].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Wang

Yue³

et al. 2019

J Ovarian Res

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Ovarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Wang

Yue³

et al. 2019

J Ovarian Res

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“…In our study, the CTC positivity rate declined rapidly during treatment and no patient showed CTCs at the end of sixth cycle of chemotherapy. In the study by Zhang et al, CTC counts decreased during adjuvant and neoadjuvant therapy as well [22]. Interestingly, peripheral blood was obtained both before and 7-14 days after surgery and a rapid increase in CTC counts has been observed between these two time points.…”

Section: Discussionmentioning

confidence: 92%

“…Possibly, not only the presence of CTCs, but their expression profiles may predict the clinical potential. Zhang et al examined blood samples from 109 patients with newly diagnosed ovarian cancer using Multiplex-RT-PCR based on the detection of six cancer-related genes [22]. While this assay yielded very high CTC detection rates of 90%, the survival analysis showed that only EpCAM positivity of CTCs predicted shorter OS.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer

Banys-Paluchowski

Fehm

Neubauer

et al. 2020

Arch Gynecol Obstet

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Purpose Presence of circulating tumor cells (CTCs) is associated with impaired clinical outcome in several solid cancers. Limited data are available on the significance of CTCs in gynaecological malignancies. The aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess their clinical relevance. Methods 43 patients with ovarian, fallopian tube and peritoneal cancer were included into this prospective study. Patients received chemotherapy according to national guidelines. CTC analysis was performed using the CellSearch system prior to chemotherapy, after three and six cycles. Results In 26% of the patients, ≥ 1CTC per 7.5 ml of blood was detected at baseline (17% of patients with de novo disease, compared to 35% in recurrent patients). Presence of CTCs did not correlate with other factors. After three cycles of therapy, CTC positivity rate declined to 4.8%. After six cycles, no patient showed persistent CTCs. Patients with ≥ 1 CTC at baseline had significantly shorter overall survival and progression-free survival compared to CTC-negative patients (OS: median 3.1 months vs. not reached, p = 0.006, PFS: median 3.1 vs. 23.1 months, p = 0.005). When only the subgroup with newly diagnosed cancer was considered, the association between CTC status and survival was not significant (OS: mean 17.4 vs. 29.0 months, p = 0.192, PFS: 14.3 vs. 26.9 months, p = 0.085). Presence of ≥ 1 CTC after three cycles predicted shorter OS in the entire patient cohort (p < 0.001). Conclusions Hematogenous tumor cell dissemination is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. CTC status before start of systemic therapy correlates with clinical outcome. Chemotherapy leads to a rapid decline in CTC counts; further research is needed to evaluate the clinical value of CTC monitoring after therapy.

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“…Following the emergence of this information regarding the potential predictive value of mesenchymal-or mixed E/M-phenotype CTCs, we developed and validated a novel custom CellSearch ® assay to assess p16 expression in the putative mixed E/M-phenotype subpopulation. Because assay validation was completed during the late stages of this trial, we performed a pilot analysis of putative mixed E/Mphenotype CTCs in 13 of the final patients enrolled, employing MUC1 as a tumor marker as has been done in several prior CTC studies [43][44][45], and enumerating and measuring p16 expression in VIM + , MUC1 + , DAPI + , and CD45cells from peripheral blood specimens. To assess all 5 markers, we implemented and validated a novel 5-color CellSearch ® assay ( Supplementary Fig.…”

Section: Characterization Of Vimentin-positive Ctcsmentioning

confidence: 99%

Intravenous 5-fluoro-2′-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors

Coyne

Wang

Zlott

et al. 2020

Cancer Chemother Pharmacol

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Purpose Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2′-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized phase 2 study to assess response to this combination in patients with advanced solid tumor types for which tumor suppressor gene methylation is potentially prognostic. To obtain pharmacodynamic evidence for DNMT inhibition by FdCyd, we developed a novel method for detecting expression of tumor suppressor protein p16/INK4A in circulating tumor cells (CTCs). Methods Patients in histology-specific strata (breast, head and neck [H&N], or non-small cell lung cancers [NSCLC] or urothelial transitional cell carcinoma) were administered FdCyd (100 mg/m 2) and THU (350 mg/m 2) intravenously 5 days/ week for 2 weeks, in 28-day cycles, and progression-free survival (PFS) rate and objective response rate (ORR) were evaluated. Blood specimens were collected for CTC analysis. Results Ninety-three eligible patients were enrolled (29 breast, 21 H&N, 25 NSCLC, and 18 urothelial). There were three partial responses. All strata were terminated early due to insufficient responses (H&N, NSCLC) or slow accrual (breast, urothelial). However, the preliminary 4-month PFS rate (42%) in the urothelial stratum exceeded the predefined goal-though the ORR (5.6%) did not. An increase in the proportion of p16-expressing cytokeratin-positive CTCs was detected in 69% of patients evaluable for clinical and CTC response, but was not significantly associated with clinical response. Conclusion Further study of FdCyd + THU is potentially warranted in urothelial carcinoma but not NSCLC or breast or H&N cancer. Increase in the proportion of p16-expressing cytokeratin-positive CTCs is a pharmacodynamic marker of FdCyd target engagement.

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Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Cited by 69 publications

References 43 publications

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer

Intravenous 5-fluoro-2′-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors

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