Subject(s)
Biomarkers, Tumor/deficiency , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Kidney/pathology , Succinate Dehydrogenase/deficiency , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Diagnosis, Differential , Humans , Kidney/metabolism , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Male , Middle AgedABSTRACT
Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome is a rare disease, and only in a minority of cases, causes an impairment of kidney function. Here, we describe a case of a 55-year-old man with a history of POEMS syndrome who presented with acute kidney injury following a routine blood test. On further investigation, a relapse in POEMS syndrome was diagnosed, uniquely isolated to renal involvement.
Subject(s)
Acute Kidney Injury/etiology , POEMS Syndrome/complications , Acute Kidney Injury/physiopathology , Humans , Kidney/physiopathology , Male , Middle Aged , POEMS Syndrome/physiopathology , RecurrenceABSTRACT
Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells.
Subject(s)
Adenocarcinoma/secondary , Biomarkers, Tumor/genetics , Cell Movement , Membrane Proteins/metabolism , Neoplasm Proteins/metabolism , Oxidoreductases/metabolism , Prostatic Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Aged , Apoptosis , Biomarkers, Tumor/metabolism , Blotting, Western , Case-Control Studies , Cell Proliferation , Disease Progression , Female , Gene Expression Profiling , Humans , Male , Membrane Proteins/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/genetics , Oligonucleotide Array Sequence Analysis , Oxidoreductases/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
Prostate cancer is the second most frequently diagnosed cancer worldwide and is the sixth leading cause of cancer deaths in men, yet it varies greatly in its aggressiveness. Currently, it is not possible to adequately differentiate between patients whose tumors will remain indolent and those patients whose disease will progress, resulting in unnecessary aggressive treatment. Consequently, there is an urgent need to identify markers of prostate cancer progression, invasiveness and metastasis to more accurately predict prognosis. The aim of this study was to assess the ability of key epithelial-to-mesenchymal transition molecules in identifying prostate cancer patients who are likely to develop aggressive tumors. Using 215 archival patient tissue samples, immunohistochemistry was applied to examine the expression and sub-cellular localization of E-Cadherin, Snail, Slug, Twist, Vimentin, BMP-2 and BMP-7. Of the seven markers assessed, a significantly increased expression of Snail protein was observed within the nucleus of prostate cancer cells and was strongly associated with increasing Gleason score and clinical stage. In addition, loss of E-Cadherin expression at the cellular membrane of prostate cancer cells was also significantly associated with increasing Gleason score, clinical stage, and additionally, a reduction in survival.
