Prostate cancer (PCa) is a highly prevalent disease, causing the second largest amount of male cancer deaths worldwide. Currently, the prostate specific antigen (PSA) blood test remains the standard serum prognostic and diagnostic monitoring biomarker but it lacks specificity and sensitivity. PSA testing can lead to invasive biopsies which can result in under detection of clinically significant disease and potential overtreatment of indolent disease. There are promising circulating biomarkers which could facilitate less invasive and more accurate tests, but present challenges in robust quantitation and deployment in clinical settings. This work presents the rapid detection of circulating YAP1 nucleic acid, androgen receptor (AR-FL) and AR-V7 mRNA for PCa prognostics in blood plasma from PCa patients. Sensitive detection of circulating YAP1 nucleic acid, AR-FL and AR-V7 mRNA extracted from PCa clinical samples was achieved with a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Optimisation of mRNA extraction methodologies for reliable detection of circulating mRNA for RT-LAMP and RT-qPCR detection took place. Multiplex testing of circulating AR-FL mRNA and YAP1 nucleic acid on an ISFET Lab-on-Chip platform was readily achieved with bio-electronic signal detection taking place within 15 min. Detection of AR-V7 and AR-FL mRNA could also be achieved simultaneously with the handheld device. Evaluation of clinical data indicated that circulating YAP1 nucleic acid presence in extracted RNA from the blood plasma of patients correlated with more advanced clinical cancer staging (p = 0.043) and PSA at diagnosis (p = 0.035). The work presents potential for Point-of-Care detection of circulating mRNA from clinical samples for PCa prognostics.

Circulating YAP1 nucleic acid and AR-FL and AR-V7 circulating mRNA were detected in the blood of prostate cancer patients within 15 min using a RT-LAMP and ISFET handheld biosensor.

Circulating YAP1 nucleic acid presence was associated with more advanced prostate cancer stage and PSA at diagnosis when detected with the ISFET biosensor. AR-FL and AR-V7 mRNA were only detected in high-risk or metastatic prostate cancer samples.

This work presents, to the authors’ knowledge, the first endogenous detection of circulating nucleic acids with an ISFET biosensor integrated onto a Lab-on-Chip device for cancer prognostics.

The authors have declared no competing interest.

This work was funded in part by a Convergence Science PhD studentship (C24523) and in part by Prostate Cancer UK grants MA-COE18-001 and Grant RIA17-ST2-017.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of Imperial College London gave ethical approval for this work. The clinical samples were recorded under the sub-collection URO CB 13 029 with the Imperial College Healthcare NHS Trust Tissue Bank.

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All data produced in the present study are available upon reasonable request to the authors.