Rapid and sensitive fusion gene detection in prostate cancer urinary specimens by label-free surface-enhanced Raman scattering

Recurrent chromosomal rearrangements such as fusion genes are associated with cancer initiation and progression. Prostate cancer (PCa) is a leading cause of cancer-related deaths in men and the TMPRSS2-ERG gene fusion is a recurrent biomarker in about 50% of all prostate cancers. However, current screening tools for TMPRSS2-ERG are generally confined to research settings and hence, the development of a rapid, sensitive and accurate assay for TMPRSS2-ERG detection may aid in clinical PCa diagnosis and treatment. Herein, we described a new strategy for non-invasive TMPRSS2-ERG detection in patient urinary samples by coupling of isothermal reverse transcription-recombinase polymerization amplification (RT-RPA) to amplify TMPRSS2-ERG transcripts and surface-enhanced Raman scattering (SERS) to directly detect the amplicons. This novel coupling of both techniques allows rapid and quantitative TMPRSS2-ERG detection. Our assay can specifically detect as low as 10³ copies input of TMPRSS2-ERG transcripts and was successfully applied to clinical PCa urinary samples. Hence, we believe our assay is a potential clinical screening tool for TMPRSS2-ERG in PCa and may have broad applications in detecting other gene fusion transcripts in other diseases.