Abstract:Patients with metastatic prostate cancer (PCa) have a poorer prognosis than patients with organ-confined tumors. We strove to uncover the proteome signature of primary PCa and associated lymph node metastases (LNMs) in order to identify proteins that may indicate or potentially promote metastases formation. We performed a proteomic comparative profiling of PCa tissue from radical prostatectomy (RPE) of patients without nodal metastases or relapse at the time of surgical resection (n = 5) to PCa tissue from RPE… Show more
“…Another group of proteins decreased in the PCa tissues was related to blood microparticles, which influence the complement and coagulation cascades and platelet degranulation. These bioinformatic results are very similar to previous proteomics studies conducted in PCa (31)(32)(33). In fact, these three protein groups, including the mitochondrial proteins, extracellularrelated proteins, and blood microparticle proteins, are known to be highly related to the occurrence of cancer.…”
Background/Aim: Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. However, there are no known molecular markers for advanced or aggressive PCa, and there is an urgent clinical need for biomarkers that can be used for prognosis and prediction of PCa. Materials and Methods: Mass spectrometry-based proteomics was used to identify new biomarkers in tissues obtained from patients with PCa who were diagnosed with T2, T3, or metastatic PCa in regional lymph nodes. Results: Among 1,904 proteins identified in the prostate tissues, 344 differentially expressed proteins were defined, of which 124 were up-regulated and 216 were down-regulated. Subsequently, based on the results of partial least squares discriminant analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we proposed that spermidine synthase (SRM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and prostacyclin synthase (PTGIS) represent new protein biomarkers for diagnosis of advanced PCa. These proteomics results were verified by immunoblot assays in metastatic PCa cell lines and by indirect enzyme-linked immunosorbent assay in prostate specimens. Conclusion: SRM was significantly increased depending on the cancer stage, confirming the possibility of using SRM as a biomarker for prognosis and prediction of advanced PCa. According to a recent report from the American Cancer Society, prostate cancer (PCa) has the highest incidence of any cancer, and the mortality arising from PCa is second among all male cancers in the USA (1). Although most PCa is found at a local or regional stage, with a 5-year survival rate of close to 100%, the 5-year survival rate for those with late-stage PCa drops sharply to 30% (2, 3). Advanced PCa, also called metastatic PCa, is an aggressive form that causes the prostatic adenocarcinoma to spread to other parts of the body, including pericapsular tissues, with lymph-node involvement, and distant metastases, which is histologically defined as stages T3 and T4 (4, 5). Overall, PCa has one of the highest incidence and mortality rates among cancers, and most of the deaths due to PCa are a result of metastasis. Thus, finding a biomarker for advanced PCa associated with metastasis and aggression is a pressing need in clinical research aimed at treating PCa. Tissue, blood, urine, and seminal fluids derived from patients are the typical sources used for the study of PCa biomarkers. Such bio-fluid samples are safe, owing to the noninvasive collection methods used, and can be collected quickly, lowering the cost of sample preparation. However, it is difficult to find low-abundance biomarkers in these samples, since most of the protein in the blood and urine is either albumin or uromodulin, respectively. In contrast, tissues collected after surgery can be used to directly observe the 195 This article is freely accessible online.
“…Another group of proteins decreased in the PCa tissues was related to blood microparticles, which influence the complement and coagulation cascades and platelet degranulation. These bioinformatic results are very similar to previous proteomics studies conducted in PCa (31)(32)(33). In fact, these three protein groups, including the mitochondrial proteins, extracellularrelated proteins, and blood microparticle proteins, are known to be highly related to the occurrence of cancer.…”
Background/Aim: Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. However, there are no known molecular markers for advanced or aggressive PCa, and there is an urgent clinical need for biomarkers that can be used for prognosis and prediction of PCa. Materials and Methods: Mass spectrometry-based proteomics was used to identify new biomarkers in tissues obtained from patients with PCa who were diagnosed with T2, T3, or metastatic PCa in regional lymph nodes. Results: Among 1,904 proteins identified in the prostate tissues, 344 differentially expressed proteins were defined, of which 124 were up-regulated and 216 were down-regulated. Subsequently, based on the results of partial least squares discriminant analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we proposed that spermidine synthase (SRM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and prostacyclin synthase (PTGIS) represent new protein biomarkers for diagnosis of advanced PCa. These proteomics results were verified by immunoblot assays in metastatic PCa cell lines and by indirect enzyme-linked immunosorbent assay in prostate specimens. Conclusion: SRM was significantly increased depending on the cancer stage, confirming the possibility of using SRM as a biomarker for prognosis and prediction of advanced PCa. According to a recent report from the American Cancer Society, prostate cancer (PCa) has the highest incidence of any cancer, and the mortality arising from PCa is second among all male cancers in the USA (1). Although most PCa is found at a local or regional stage, with a 5-year survival rate of close to 100%, the 5-year survival rate for those with late-stage PCa drops sharply to 30% (2, 3). Advanced PCa, also called metastatic PCa, is an aggressive form that causes the prostatic adenocarcinoma to spread to other parts of the body, including pericapsular tissues, with lymph-node involvement, and distant metastases, which is histologically defined as stages T3 and T4 (4, 5). Overall, PCa has one of the highest incidence and mortality rates among cancers, and most of the deaths due to PCa are a result of metastasis. Thus, finding a biomarker for advanced PCa associated with metastasis and aggression is a pressing need in clinical research aimed at treating PCa. Tissue, blood, urine, and seminal fluids derived from patients are the typical sources used for the study of PCa biomarkers. Such bio-fluid samples are safe, owing to the noninvasive collection methods used, and can be collected quickly, lowering the cost of sample preparation. However, it is difficult to find low-abundance biomarkers in these samples, since most of the protein in the blood and urine is either albumin or uromodulin, respectively. In contrast, tissues collected after surgery can be used to directly observe the 195 This article is freely accessible online.
“…This number is in the range of several other FFPE-based proteomic studies [30], [31], [33]. Limited proteome overlap between biological and technical replicates continues to be a characteristic limitation of explorative shotgun proteomics [26], [27].…”
Section: Resultsmentioning
confidence: 98%
“…We employed FFPE tissue samples since these represent the standard tissue for histopathological diagnosis and evaluation of human malignancies. Proteomic analysis of FFPE tissues using “direct trypsinization with acid-labile surfactants” demonstrated robustness in protein identification and quantification [30], [31].Figure 1Schematic representation of the experimental design used in this proteomics study.…”
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) and Monoamine Oxidase A (MAOA) in the short PFS cohort, which were corroborated by immunohistochemistry. In vitro, specific inhibition of ALDH1A1 by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. In MiaPaCa-2 cells, ALDH1A1 silencing sensitized cells towards treatment with gemcitabine, radiation or chemoradiation. In Panc 05.04, increased cell death was observed upon gemcitabine treatment only. These findings are in line with previous studies that have suggested a role of ALDH1A1 chemoradiation resistance, e.g., in esophageal cancer. In summary, we present one of the first proteome studies to investigate the responsiveness of PDAC to chemoradiation and provide further evidence for a role of ALDH1A1 in therapy resistance.
“…However, proteomic profiling is gaining interest for the investigation of malignancies due to the limited correlation between mRNA and protein levels [ 13 , 14 ]. Formalin-fixed, paraffin-embedded (FFPE) samples are a valuable resource for proteomic profiling [ 15 – 17 ], enabling retrospective profiling of clinic-pathologically annotated specimens [ 18 , 19 ]. In the present study, we employed “FFPE proteomics” for the differential proteomic profiling of RO and chRCC cases for which we find noticeable differences.…”
BackgroundRenal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.MethodsWe employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.ResultsAt 1% false discovery rate, we identified > 3900 proteins, of which > 2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.ConclusionWe present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9200-6) contains supplementary material, which is available to authorized users.
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