Abstract
Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate cancer exist. Using an unbiased, quantitative approach, this study evaluates the potential of three proteins of the 40S ribosomal protein complex as putative biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi-automated Ox-DAB signal quantification using ImageJ software revealed a significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non-malignant tissue (p<0.0001). Receiver operating characteristics curves were calculated to evaluate the potential of each protein as a biomarker of malignancy in prostate cancer. Positive likelihood ratios for RPS19, RPS21 and RPS24 were calculated as 2.99, 4.21, and 2.56 respectively, indicating that the overexpression of the protein is correlated with the presence of disease. Triple-labelled, quantitative, immunofluorescence (with RPS19, RPS21 and RPS24) showed significant changes (p<0.01) in the global intersection coefficient, a measure of how often two fluorophore signals intersect, for RPS19 and RPS24 only. No change was observed in the co-localization of any other permutations of the three proteins. Our results show that RPS19, RPS21 or RPS24 are upregulated in malignant tissue and may serve as putative biomarkers for prostate cancer.
Highlights
Prostate cancer (CaP) is the second most diagnosed cancer in men, with an estimated 1.1 million new cases of the disease worldwide in 2012 [1]
Our results show ribosomal protein expression of RPS19, RPS21 and RPS24 is dysregulated in human CaP and increased expression of RPS19 and RPS21 is seen in high Gleason grade CaP that may provide an avenue for developing these as CaP prognostic biomarkers
Sparse literature exists regarding the expression of ribosomal genes or proteins in cancer, expression levels of genes coding for ribosomal proteins show large variation across different tissues [24]
Summary
Prostate cancer (CaP) is the second most diagnosed cancer in men, with an estimated 1.1 million new cases of the disease worldwide in 2012 [1]. A biopsy with pathological analysis is the main modality of diagnosis of CaP, with transrectal ultrasound-guided prostate biopsy procedures used as the current method of obtaining a prostate tissue sample [5]. The current diagnostic modalities have drawbacks, such as under sampling, or pathological reporting variation [6]. We have previously used largescale tissue arrays to identify proteins that are differentially expressed in non-malignant vs malignant samples using a reproducible and quantitative approach [7, 8], rather than utilising a subjective interpretation of immunohistochemical expression. We have applied the quantitative approach to a tissue array containing 245 human prostate tissue samples, gathered from 82 patients, stained for ribosomal (RPS) proteins
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