Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

Wang, Haiying; Molina, Julian R.; Jiang, Jian-Tang; Ferber, Matthew J.; Pruthi, Sandhya; Jatkoe, Tim; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jianming; Wang, Yixin

doi:10.3892/mco.2013.163

Cited by 12 publications

(7 citation statements)

References 20 publications

(30 reference statements)

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“…In our study, of the 9 cases of MBC patients that have high level of TFF1 mRNA, there were 7 cases with bone metastasis (77.8%). This is in agreement with the study of Wang et al [ 30 ] who found that 43.3% of patients with bone metastasis exhibited a high expression level of TFF1. Similarly, Smid et al [ 31 ] considered TFF1 most differentially expressed gene (P < .0015) in breast cancer metastasis to bone.…”

Section: Discussionsupporting

confidence: 94%

TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

Elnagdy

Farouk

Seleem

et al. 2018

Journal of Oncology

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Introduction Breast cancer metastasis occurs when tumor cells dissociate from the primary tumor and migrate to distant organs through the peripheral bloodstream or lymphatic drainage. Circulating tumor cells (CTCs) originate from primary sites or metastases and circulate in the patients' bloodstream. Molecular assays for the detection and molecular characterization of CTCs can serve as a liquid biopsy and can represent an alternative to invasive biopsies as a source of tumor tissue in the metastatic patients. Patients and Methods We analyzed the presence of CTCs in the peripheral blood of 50 breast cancer patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) to detect trefoil factor family (TFF) 1 and 3 genes. Results We found significant difference in the level of both TFF1 and TFF3 mRNA in the blood of nonmetastatic versus metastatic breast cancer patients (p= 0.001 and p= 0.038, respectively). TFF1 mRNA was detected at higher levels in 34.6% of metastatic breast cancer patients as compared to 0% of nonmetastatic (p= 0.002). As regards TFF3 mRNA, it was detected at higher levels in 46.2% of metastatic breast cancer patients as compared to 4% of nonmetastatic (p= 0.026). Moreover, we found that the high level of both TFF1 and TFF3 mRNA was related to estrogen status of the patients. The detection of high level of TFF1 mRNA in CTCs was associated with bone metastases (77.8%), while that of TFF3 was related to lymph node involvement (75%) and lung metastases (68.8%). Conclusion The combined measurement of both TFF1 and TFF3 mRNA level for differentiation of metastatic from nonmetastatic breast cancer gave 57.69% sensitivity and 83.3% specificity.

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Section: Discussionsupporting

confidence: 94%

TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

Elnagdy

Farouk

Seleem

et al. 2018

Journal of Oncology

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“…A comparison of the expression profiles in bone-metastatic human breast cancer sublines with the parental cell line identified several mediators of bone metastases, in particular CXCR4, IL-11, OPN and MMP1, the combination of which are sufficient to enhance osteolytic metastases when overexpressed in the parental cell line [41]. Subsequently, several other profiling and microarray studies have been published using different types of tumor cells, revealing a number of other potentially important bone metastasis targets that require further functional characterization in future research [42, 43, 44, 45]. …”

Section: Cancer Invasionmentioning

confidence: 99%

New therapeutic targets for cancer bone metastasis

Krzeszinski

Wan

2015

Trends in Pharmacological Sciences

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Bone metastases are dejected consequences of many types of tumors including breast, prostate, lung, kidney and thyroid cancers. This complicated process begins with the successful tumor cell epithelial–mesenchymal transition, escape from the original site, and penetration into circulation. The homing of tumor cells to the bone depends on both tumor-intrinsic traits and various molecules supplied by the bone metastatic niche. The colonization and growth of cancer cells in the osseous environment, which awaken their dormancy to form micro- and macro-metastasis, involve an intricate interaction between the circulating tumor cells and local bone cells including osteoclasts, osteoblasts, adipocytes and macrophages. In this review, we discuss the most recent advances in the identification of new molecules and novel mechanisms during each step of bone metastasis that may serve as promising therapeutic targets.

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“…Another group [ 132 ] performed with the CellSearch ® system both the enumeration of CTCs, by immunostaining for cytokeratins and CD45, and the molecular analysis of cells bound to EpCAM-coated ferrofluids and retrieved from the CellSearch ® system cartridge. Gene expression profile of blood samples from metastatic breast cancer (61% positivity) and from healthy donors enriched for EpCAM+ cells by the CellSearch ® system were performed by RT-qPCR of a panel including 1 epithelial cell-specific and 22 breast-specific genes.…”

Section: Ctc Gene Expression Profile Studies In Breast Cancermentioning

confidence: 99%

“…Epithelial and breast cancer-related genes failed to predict response to therapy and disease progression when assessed in EpCAM-based enriched CTCs in patients with metastatic breast cancer starting first-line cisplatin-based therapy or treated with anthracycline and taxane [ 135 , 159 , 165 ]. However, some genes peculiar to luminal breast cancer are associated to the site of metastasis or response to endocrine therapy, such as TFF1 , a classical estrogen-regulated gene, whose expression in CTCs was found to be a strong predictor of bone metastasis [ 132 ]. Hormonal receptor status in CTCs might have a predictive role, as patients with high expression of estrogen receptor β gene ESR2 in CTCs exhibited better response to hormonal treatment, and patients with ER-negative primary tumors and ER-positive CTCs had a longer median time to treatment switch compared to those with concordantly ER-negative CTCs [ 132 , 165 ].…”

Section: Ctc Gene Expression Profile Studies In Breast Cancermentioning

confidence: 99%

“…However, some genes peculiar to luminal breast cancer are associated to the site of metastasis or response to endocrine therapy, such as TFF1 , a classical estrogen-regulated gene, whose expression in CTCs was found to be a strong predictor of bone metastasis [ 132 ]. Hormonal receptor status in CTCs might have a predictive role, as patients with high expression of estrogen receptor β gene ESR2 in CTCs exhibited better response to hormonal treatment, and patients with ER-negative primary tumors and ER-positive CTCs had a longer median time to treatment switch compared to those with concordantly ER-negative CTCs [ 132 , 165 ]. Two 8-gene signatures able to predict response to therapy, and overall including CXCL14 , KRT7 , KRT19 , KRT81 , PKP3 , PTRF , TIMP3 , LAD1 , S100A16 , FKBP10 , TWIST1 , PTRF , EEF1A2 , PTPRK , EGFR and ERBB3 genes, were generated by comparing the CTC profile of poor and good responders following first line treatment with standard hormonal or chemotherapy or with aromatase inhibitors only [ 166 , 167 ].…”

Section: Ctc Gene Expression Profile Studies In Breast Cancermentioning

confidence: 99%

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Signatures of Breast Cancer Progression in the Blood: What Could Be Learned from Circulating Tumor Cell Transcriptomes

Fina

2022

Cancers

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Gene expression profiling has revolutionized our understanding of cancer biology, showing an unprecedented ability to impact patient management especially in breast cancer. The vast majority of breast cancer gene expression signatures derive from the analysis of the tumor bulk, an experimental approach that limits the possibility to dissect breast cancer heterogeneity thoroughly and might miss the message hidden in biologically and clinically relevant cell populations. During disease progression or upon selective pressures, cancer cells undergo continuous transcriptional changes, which inevitably affect tumor heterogeneity, response to therapy and tendency to disseminate. Therefore, metastasis-associated signatures and transcriptome-wide gene expression measurement at single-cell resolution hold great promise for the future of breast cancer clinical care. Seen from this perspective, transcriptomics of circulating tumor cells (CTCs) represent an attractive opportunity to bridge the knowledge gap and develop novel biomarkers. This review summarizes the current state-of-the-science on CTC gene expression analysis in breast cancer, addresses technical and clinical issues related to the application of CTC-derived signatures, and discusses potential research directions.

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Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

Abstract: Abstract. Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients.

Cited by 12 publications

References 20 publications

TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

New therapeutic targets for cancer bone metastasis

Signatures of Breast Cancer Progression in the Blood: What Could Be Learned from Circulating Tumor Cell Transcriptomes

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