2014–2017 Clinical Study Programme

Development of Diagnostic Gene Signature

 

Caldera Health started the search for prostate cancer biomarkers with next-generation sequence analysis of prostate tissue.

1000 Men, Aged 60-69, 4.89% Prevalance of Prostate Cancer

Clinical Study 1: Completed in 2014

Screening of 84 RNA biomarkers and three reference biomarkers using RNA extracted from formalin-fixed and paraffin-embedded (FFPE, a standard clinical procedure) prostatectomy tissue from a total of 42 donors.   One Auckland Hospital histopathologist reviewed FFPE blocks for entry to the study and identified cancerous and healthy areas for analysis.

Using a patented discovery process, Caldera was able to measure gene transcripts that were either elevated or diminished in prostate cancer prostatectomy samples as compared to healthy tissue. Significant differential expression could be detected in 60 of the screened biomarkers.

From these 60 RNA biomarkers, the 35 best performing biomarkers were chosen to go forward in the next clinical study.

Clinical Study 2: Completed in 2016

Completed in June 2016 using the 35 selected biomarkers. This study compared prostate biopsy tissue without evidence of cancer with tumour tissue isolated from positive biopsies to identify gene signatures that are able to determine the presence of prostate cancer.

From a total of 142 samples, a lead gene signature was identified comprising a small number of genes with a sensitivity of 92% and specificity of 95%. As there were multiple, highly accurate gene signatures, 20 biomarkers able to form multiple gene signatures were selected for the validation study.

Clinical Study 2B: Completed in 2016

Clinical Study 2B was divided into two parts: an initial independent validation on 157 samples and a second, blinded, independent validation on 95 samples.

Completed in August 2016, 20 biomarkers were analysed for 157 biopsy samples either from men with no evidence of cancer (negative biopsies) or from tumour tissue isolated from positive biopsies. The results allowed selection of the most accurate diagnostic gene signature (trained using Clinical Study 2 data), with a sensitivity of 98% and specificity of 99%. The number of biomarkers required were significantly reduced.

In December 2016, the blinded study of 95 additional independent samples was completed. Analysis confirmed the high accuracy of the lead diagnostic signature with only 4 misclassifications.

This finalised Clinical Study 2B, with a total of 252 independent validation samples, yielding an overall sensitivity of 97% and specificity of 97% for the diagnosis of prostate cancer.

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