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Identification of a blood-borne miRNA signature of synovial sarcoma.

Fricke A, Ullrich PV, Heinz J, Pfeifer D, Scholber J, Herget GW, Hauschild O, Bronsert P, Stark GB, Bannasch H, Eisenhardt SU, Braig D - Mol. Cancer (2015)

Bottom Line: The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients.Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. alba.fricke@uniklinik-freiburg.de.

ABSTRACT

Background: Synovial sarcoma account for approximately 10 % of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).

Methods: Blood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients.

Results: Unsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission.

Conclusion: Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.

No MeSH data available.


Related in: MedlinePlus

Change in miRNA-expression at remission as well as when presenting active disease in two individual synovial sarcoma patients. a. Patient 1 initially presented with localized disease of the lower extremity. miRNA levels were recorded 1 day before surgery and at three time-points after complete tumor resection. b. Patient 2 was in complete remission but developed pulmonary metastasis 4 months after the initial blood withdrawal
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Fig4: Change in miRNA-expression at remission as well as when presenting active disease in two individual synovial sarcoma patients. a. Patient 1 initially presented with localized disease of the lower extremity. miRNA levels were recorded 1 day before surgery and at three time-points after complete tumor resection. b. Patient 2 was in complete remission but developed pulmonary metastasis 4 months after the initial blood withdrawal

Mentions: To exclude a bias of fundamental expression levels of miRNAs among the individual patients with synovial sarcoma and to illustrate the change of miRNA expression at remission and in active disease, we performed a matched-pair analysis in two individual sarcoma patients. Patient 1 initially presented with localized disease of the lower extremity. The miRNA-expression before surgical resection of the tumor as well as two weeks, three months and ten months after complete surgical removal of the tumor was analyzed. The miRNA expression levels decreased rapidly after tumor resection (Fig. 4). Patient 2 was part of the synovial sarcoma in remission cohort at first with unsuspicious miRNA levels. However, she developed pulmonary metastases four months after the initial blood withdrawal. The 2nd blood withdrawal was carried out 5 month after the 1st blood withdrawal. At this time, the miRNA expression levels were significantly elevated when compared to their expression at the time of remission (Fig. 4). Thus, by performing a matched-pair analysis in these two individual sarcoma patients, we were able to illustrate the downregulation of miRNA expression at remission as well as the upregulation of the presented miRNAs in reoccurring active disease.Fig. 4


Identification of a blood-borne miRNA signature of synovial sarcoma.

Fricke A, Ullrich PV, Heinz J, Pfeifer D, Scholber J, Herget GW, Hauschild O, Bronsert P, Stark GB, Bannasch H, Eisenhardt SU, Braig D - Mol. Cancer (2015)

Change in miRNA-expression at remission as well as when presenting active disease in two individual synovial sarcoma patients. a. Patient 1 initially presented with localized disease of the lower extremity. miRNA levels were recorded 1 day before surgery and at three time-points after complete tumor resection. b. Patient 2 was in complete remission but developed pulmonary metastasis 4 months after the initial blood withdrawal
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4528907&req=5

Fig4: Change in miRNA-expression at remission as well as when presenting active disease in two individual synovial sarcoma patients. a. Patient 1 initially presented with localized disease of the lower extremity. miRNA levels were recorded 1 day before surgery and at three time-points after complete tumor resection. b. Patient 2 was in complete remission but developed pulmonary metastasis 4 months after the initial blood withdrawal
Mentions: To exclude a bias of fundamental expression levels of miRNAs among the individual patients with synovial sarcoma and to illustrate the change of miRNA expression at remission and in active disease, we performed a matched-pair analysis in two individual sarcoma patients. Patient 1 initially presented with localized disease of the lower extremity. The miRNA-expression before surgical resection of the tumor as well as two weeks, three months and ten months after complete surgical removal of the tumor was analyzed. The miRNA expression levels decreased rapidly after tumor resection (Fig. 4). Patient 2 was part of the synovial sarcoma in remission cohort at first with unsuspicious miRNA levels. However, she developed pulmonary metastases four months after the initial blood withdrawal. The 2nd blood withdrawal was carried out 5 month after the 1st blood withdrawal. At this time, the miRNA expression levels were significantly elevated when compared to their expression at the time of remission (Fig. 4). Thus, by performing a matched-pair analysis in these two individual sarcoma patients, we were able to illustrate the downregulation of miRNA expression at remission as well as the upregulation of the presented miRNAs in reoccurring active disease.Fig. 4

Bottom Line: The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients.Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. alba.fricke@uniklinik-freiburg.de.

ABSTRACT

Background: Synovial sarcoma account for approximately 10 % of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).

Methods: Blood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients.

Results: Unsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission.

Conclusion: Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.

No MeSH data available.


Related in: MedlinePlus