Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours

Abstract Background Liquid biopsy, which facilitates minimally invasive analysis of body fluid samples, has considerable potential as a diagnostic and prognostic tool in various cancers. Analysis of circulating tumour cells, circulating tumour DNA, and exosomes in liquid biopsies has advantages and...

Full description

Saved in:
Bibliographic Details
Main Authors: Naoki Furukawa, Nobuhiko Hasegawa, Daisuke Kubota, Yasuhiro Nakamura, Hirokazu Tanaka, Shintaro Iwata, Akira Kawai, Tsuyoshi Saito, Tatsuya Takagi, Shinji Kohsaka, Muneaki Ishijima
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-025-13950-2
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849765411413819392
author Naoki Furukawa
Nobuhiko Hasegawa
Daisuke Kubota
Yasuhiro Nakamura
Hirokazu Tanaka
Shintaro Iwata
Akira Kawai
Tsuyoshi Saito
Tatsuya Takagi
Shinji Kohsaka
Muneaki Ishijima
author_facet Naoki Furukawa
Nobuhiko Hasegawa
Daisuke Kubota
Yasuhiro Nakamura
Hirokazu Tanaka
Shintaro Iwata
Akira Kawai
Tsuyoshi Saito
Tatsuya Takagi
Shinji Kohsaka
Muneaki Ishijima
author_sort Naoki Furukawa
collection DOAJ
description Abstract Background Liquid biopsy, which facilitates minimally invasive analysis of body fluid samples, has considerable potential as a diagnostic and prognostic tool in various cancers. Analysis of circulating tumour cells, circulating tumour DNA, and exosomes in liquid biopsies has advantages and disadvantages. However, their utility in rare cancers, such as malignant bone and soft tissue tumours, remains unknown. In this study, we examined the levels of circulating cell-free tumour RNA (cfRNA) in the blood of patients with malignant bone and soft tissue tumours harbouring specific fusion genes, to explore the relationship between fusion gene expression in the blood and therapeutic response and disease status, and to validate the clinical utility of liquid biopsy. Methods The study involved 3 cases (7 samples) of Ewing’s sarcoma, 6 cases (12 samples) of myxoid liposarcoma, and 1 case (2 samples) of synovial sarcoma with specific fusion genes. Fusion gene analysis was performed using tumour tissue samples to identify breakpoints. Primers for liquid biopsy were designed based on the fusion genes identified. cfRNA was extracted from each patient’s plasma and used for reverse transcription polymerase chain reaction (RT-PCR) with the designed primers. The RT-PCR product was subjected to Sanger sequencing. Results Fusion gene breakpoints were identified in 10 samples from 6 cases. The fusion gene detection rate in the blood was 100% at both naïve status and symptom exacerbation in patients with Stage IV disease. In patients with Stage III disease progressing to Stage IV, the fusion gene was detected in the blood prior to imaging tests. Conclusions The detection of specific fusion genes from cfRNAs shows potential for monitoring the progression of fusion-related sarcomas in the context of chemotherapy.
format Article
id doaj-art-61c7e39331e847b2a56018946b9010aa
institution DOAJ
issn 1471-2407
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj-art-61c7e39331e847b2a56018946b9010aa2025-08-20T03:04:51ZengBMCBMC Cancer1471-24072025-04-0125111110.1186/s12885-025-13950-2Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumoursNaoki Furukawa0Nobuhiko Hasegawa1Daisuke Kubota2Yasuhiro Nakamura3Hirokazu Tanaka4Shintaro Iwata5Akira Kawai6Tsuyoshi Saito7Tatsuya Takagi8Shinji Kohsaka9Muneaki Ishijima10Department of Orthopaedics, Faculty of Medicine, Juntendo UniversityDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityDepartment of Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center HospitalDepartment of Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center HospitalDepartment of Human Pathology, Juntendo University School of MedicineDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityDivision of Cellular Signaling, National Cancer Center Research InstituteDepartment of Orthopaedics, Faculty of Medicine, Juntendo UniversityAbstract Background Liquid biopsy, which facilitates minimally invasive analysis of body fluid samples, has considerable potential as a diagnostic and prognostic tool in various cancers. Analysis of circulating tumour cells, circulating tumour DNA, and exosomes in liquid biopsies has advantages and disadvantages. However, their utility in rare cancers, such as malignant bone and soft tissue tumours, remains unknown. In this study, we examined the levels of circulating cell-free tumour RNA (cfRNA) in the blood of patients with malignant bone and soft tissue tumours harbouring specific fusion genes, to explore the relationship between fusion gene expression in the blood and therapeutic response and disease status, and to validate the clinical utility of liquid biopsy. Methods The study involved 3 cases (7 samples) of Ewing’s sarcoma, 6 cases (12 samples) of myxoid liposarcoma, and 1 case (2 samples) of synovial sarcoma with specific fusion genes. Fusion gene analysis was performed using tumour tissue samples to identify breakpoints. Primers for liquid biopsy were designed based on the fusion genes identified. cfRNA was extracted from each patient’s plasma and used for reverse transcription polymerase chain reaction (RT-PCR) with the designed primers. The RT-PCR product was subjected to Sanger sequencing. Results Fusion gene breakpoints were identified in 10 samples from 6 cases. The fusion gene detection rate in the blood was 100% at both naïve status and symptom exacerbation in patients with Stage IV disease. In patients with Stage III disease progressing to Stage IV, the fusion gene was detected in the blood prior to imaging tests. Conclusions The detection of specific fusion genes from cfRNAs shows potential for monitoring the progression of fusion-related sarcomas in the context of chemotherapy.https://doi.org/10.1186/s12885-025-13950-2Cell-free RNAFusion geneLiquid biopsyMalignant bone and soft tissue tumour
spellingShingle Naoki Furukawa
Nobuhiko Hasegawa
Daisuke Kubota
Yasuhiro Nakamura
Hirokazu Tanaka
Shintaro Iwata
Akira Kawai
Tsuyoshi Saito
Tatsuya Takagi
Shinji Kohsaka
Muneaki Ishijima
Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
BMC Cancer
Cell-free RNA
Fusion gene
Liquid biopsy
Malignant bone and soft tissue tumour
title Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
title_full Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
title_fullStr Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
title_full_unstemmed Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
title_short Prognostic potential of fusion gene analysis using plasma cell-free RNA in malignant bone and soft tissue tumours
title_sort prognostic potential of fusion gene analysis using plasma cell free rna in malignant bone and soft tissue tumours
topic Cell-free RNA
Fusion gene
Liquid biopsy
Malignant bone and soft tissue tumour
url https://doi.org/10.1186/s12885-025-13950-2
work_keys_str_mv AT naokifurukawa prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT nobuhikohasegawa prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT daisukekubota prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT yasuhironakamura prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT hirokazutanaka prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT shintaroiwata prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT akirakawai prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT tsuyoshisaito prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT tatsuyatakagi prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT shinjikohsaka prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours
AT muneakiishijima prognosticpotentialoffusiongeneanalysisusingplasmacellfreernainmalignantboneandsofttissuetumours