A proteomic glimpse into the oncogenesis of prostate cancer

Abstract

Prostate cancer (PCa) is the second most frequent cancer in men worldwide. Distinguishing between the nonaggressive and aggressive forms of this disease is difficult, and a means to better characterize molecular patterns that could aid in diagnosis is urgently needed. Here, we compare the proteomic profiles of PCa and benign prostatic hyperplasia (BPH) in an effort to elucidate underlying mechanisms of oncogenesis. We compared protein expression in PCa and BPH tissue biopsies using quantitative tandem mass tag (TMT) and a MultiNotch data acquisition proteomic on an Orbitrap Fusion. Four proteins that were observed to be differentially abundant in the mass spectrometry analysis were selected for further comparison with quantitative real-time PCR: S100A4, L-lactate dehydrogenase B-chain (LDHB), Phosphatidylethanolamine-binding-protein 1-RAF (RKIP), and Ras suppressor-protein-1 (RSU1). Mass spectrometry showed RKIP and RSU1 to be upregulated in PCa, while S100A4 and LDHB were upregulated in BPH. q-PCR results were in agreement with quantitative proteomic data in BPH tissue but disagree with gene expression analysis of PCa samples. These four elements showed higher gene expression in BPH than in PCa. Taken together, our results complement and reinforce the current understanding of prostate cancer progression.

Targeting the Metabolic Paradigms in Cancer and Diabetes

“…Nevertheless, two features of the Warburg effect remain unaltered: increased glucose uptake and lactate production [6,7]. Aerobic glycolysis is markedly heightened in over 70% of cancer types, such as lung [8], breast [9], liver [10,11], brain [12], prostate [13], gynecologic [14], and pancreatic cancer [4,15,16]. Similar to solid tumors, hematologic malignancies, such as lymphomas [16][17][18] and leukemias [16,19,20], also demonstrate high aerobic glycolysis and low OXPHOS rates.…”

Targeting the Metabolic Paradigms in Cancer and Diabetes

“…Nevertheless, the two following features remain unaltered with regard to the Warburg effect: increased glucose uptake and lactate production [5,6]. Aerobic glycolysis is markedly heightened in over 70% of cancer types such as lung [7], breast [8], liver [9,10], brain [11], prostate [12], gynecologic [13], and pancreatic cancer [3,14,15]. Similar to solid tumors, hematologic malignancies, such as lymphomas [15][16][17] and leukemias [15,18,19], also demonstrate high aerobic glycolysis and low OXPHOS rates.…”