Liquid biopsy: miRNA as a potential biomarker in oral cancer

Oral cancer is one of the leading cancers in South-Asian countries. Despite the easy access of the oral cavity, the detection and five year survival rates of OSCC patients are dismal. Identification of non-invasive biomarkers to determine the progression and recurrence of OSCC could be of immense help to patients. Recent studies on oral cancer suggest the importance of non-invasive biomarker development. Micro-RNAs (miRNAs) are one of the important components of the cell-free nucleic acids available in different body fluids. Here, we have reviewed the current understanding of circulating miRNAs as non-invasive biomarkers in different body fluids of oral cancer patients. A number of circulating miRNAs are found to be common in the body fluids of OSCC patients, while many of these are study specific, the possible sources of this variability could be due to differences in sample processing, assay procedure, clinical stage of the disease, oral habit and environmental factors. The prognostic and therapeutic significance of these circulating miRNAs are suggested by several studies. Mir-371, mir-150, mir-21 and mir-7d were found to be potential prognostic markers, while mir-134, mir-146a, mir-338 and mir-371 were associated with metastases. The prognostic markers, mir-21 and mir-7d were also found to be significantly correlated with resistance to chemotherapy, while mir-375, mir-196 and mir-125b were significantly correlated with sensitivity to radiotherapy. Despite the promising roles of circulating miRNAs, challenges still remain in unravelling the exact regulation of these miRNAs before using them for targeted therapy.     

Exosome circ_0044516 promotes prostate cancer cell proliferation and metastasis as a potential biomarker

Circular RNAs (circRNAs) are important regulators in cancer growth and progression. Exosomes carry various molecules including RNA, protein, and lipid from one cell to another cell. But the role of circRNAs from the exosomes from prostate cancer patients are not elucidated. In this study, circ_0044516 was found upregulated in prostate cancer and the roles and molecular mechanism of Hsa_circ_0044516 (circ_0044516) was investigated. Firstly, the exosomes of prostate cancer patients were collected for human circRNAs microarray to screen the circRNA expression profile. There were 35 significantly expressed circRNAs with more than fivefolds from microarray analysis. Circ_0044516 was verified to be significantly upregulated in the exosomes from prostate cancer patients and the cell lines. Further investigation demonstrated that circ_0044516 downregulation inhibited the proliferation and metastasis of prostate cancer cells. By bioinformatics and luciferase reporter assays, circ_0044516 was verified to downregulate miR-29a-3p expression and negatively related to miR-29a-3p expression levels in prostate cancer. In a summary, the study indicated that circ_0044516 played an important role in prostate cancer cell survival and metastasis, which suggested that an oncogenic role of circ_0044516 in prostate cancer.     

Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis

Bladder cancer is clinically characterized by high recurrent rate and poor prognosis and thereby patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method for detecting and monitoring bladder cancer would thus be advantageous. In this study, by using the two-dimensional electrophoresis (2-DE) approach with subsequent mass spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1 (Apo-A1) in individual urine from patients with bladder cancer, which was confirmed by Western blot results. A further analysis of the urinary Apo-A1 levels by an enzyme-linked immunosorbent assay yielded results that were consistent with the Western blot, and suggested Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from healthy controls at 19.21 ng/ml. Further validation assay in a larger number of urine samples (n = 379) showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could significantly increased the sensitivity in detecting bladder cancer. Our data showed a significant relationship of expressed Apo-A1 was established between bladder cancer and normal controls. Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.     

Heat-shock protein 27: a potential biomarker for hepatocellular carcinoma identified by serum proteome analysis

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and ranks second in China. The prognosis of HCC remains dismal mainly because of its late diagnosis, especially in patients with coexisting chronic liver diseases. To identify serum biomarkers for HCC, sera from 20 healthy volunteers, 20 hepatitis B virus (HBV) infected patients and 20 HCC patients were selected for screening study and same number of sera into the same three groups were used for validation study. A strategy including sonication, albumin and immunoglobulin G (IgG) depletion and desalting was optimized for screening differentially expressed proteins of low abundance in serum. By 2-DE image analysis and MALDI-TOF-MS/MS identification, eight proteins including heat-shock protein 27 (HSP27), alpha-fetoprotein (AFP), alpha-1 antitrypsin, clusterin, caeruloplasmin, haptoglobin alpha2 chain, tranferrin and transthyretin were found significantly changed among the healthy, HBV and HCC groups. Further validation study by Western blot showed the detection of HSP27 in 90% HCC sera and two HBV sera, but in none of normal sera. Thus, 2-DE based serum proteome analysis can be useful in the screening of serum biomarkers for HCC and HSP27 could aid in the diagnosis of HCC though further validation is needed.     

Calreticulin as a potential diagnostic biomarker for lung cancer

Calreticulin (CRT) is an endoplasmic reticulum luminal Ca(2+)-binding chaperone protein. By immunizing mice with recombinant fragment (rCRT/39-272), six clones of monoclonal antibodies (mAbs) were generated and characterized. Based on these mAbs, a microplate chemiluminescent enzyme immunoassay (CLEIA) system with a measured limit of detection of 0.09?ng/ml was developed. Using this CLEIA system, it was found that soluble CRT (sCRT) level in serum samples from 58 lung cancer patients was significantly higher than that from 40 healthy individuals (only 9 were detectable, P?相似文献   

Integrated bioinformatics analysis identified MTHFD1L as a potential biomarker and correlated with immune infiltrates in hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is one of the most frequently occurring primary malignant liver tumors and seriously harms people’s health in the world. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) has been shown to be associated with colon cancer cell proliferation, colony formation and invasion. In the present study, a total of 370 LIHC and 51 normal samples data were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatics and immunohistochemistry (IHC) analysis showed that MTHFD1L is highly expressed in liver tumors. Correlation analysis suggested the differences of vital status between high- and low-expression MTHFD1L groups of LIHC. Univariate and multivariate Cox proportional hazards regression were performed to identify the relationship between clinical characteristics and overall survival (OS). In addition, to explore whether MTHFD1L has an effect on the immune infiltration of LIHC. The correlation between MTHFD1L expression and 24 immune cells were analyzed by ImmuneCellAI database. Furthermore, we combined three databases CIBERSORT, TIMER and ImmuneCellAI to do a comprehensive validation and determined that dendritic cells (DCs) resting, macrophage M0 and macrophage M2 closely related to the expression of MTHFD1L. The results showed that MTHFD1L was a potential prognostic biomarker for LIHC, and could help to elucidate that how the immune microenvironment promotes liver cancer development.     

GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer

Somatic hypermethylation of CpG island sequences at GSTP1, the gene encoding the pi-class glutathione S-transferase, appears to be characteristic of human prostatic carcinogenesis. To consider the potential utility of this epigenetic alteration as a biomarker for prostate cancer, we present here a comprehensive review of the literature describing somatic GSTP1 changes in DNA from prostate cells and tissues. GSTP1 CpG island hypermethylation has been detected in prostate cancer DNA using a variety of assay techniques, including (i) Southern blot analysis (SB), after treatment with (5-m)C-sensitive restriction endonucleases, (ii) the polymerase chain reaction, following treatment with (5-m)C-sensitive restriction endonucleases (RE-PCR), (iii) bisulfite genomic sequencing (BGS), and (iv) bisulfite modification followed by the polymerase chain reaction, using primers selective for target sequences containing (5-m)C (MSP). In the majority of the case series so far reported, GSTP1 CpG island hypermethylation was present in DNA from at least 90% of prostate cancer cases. When analyses have been carefully conducted, GSTP1 CpG island hypermethylation has not been found in DNA from normal prostate tissues, or from benign prostatic hyperplasia (BPH) tissues, though GSTP1 CpG island hypermethylation changes have been detected in DNA from candidate prostate cancer precursor lesions proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN). Using PCR methods, GSTP1 CpG island hypermethylation has also been detected in urine, ejaculate, and plasma from men with prostate cancer. GSTP1 CpG island hypermethylation, a somatic epigenetic alteration, appears poised to serve as a molecular biomarker useful for prostate cancer screening, detection, and diagnosis.     

A potential biomarker of kidney damage identified by proteomics: preliminary findings

4-Aminophenol (4-AP) and d-serine are established rodent nephrotoxins that selectively damage renal proximal tubules. In an attempt to understand the mechanism of action of these toxicants in greater detail, a high throughput proteomics approach was used to profile protein changes in the plasma of animals treated with these compounds. Male Fischer 344 and Alderley Park rats were treated with increasing doses of 4-AP or d-serine and plasma samples were collected over time. Control groups received either saline or the non-toxic enantiomer, l-serine. Using high throughput two-dimensional gel analysis, a number of plasma proteins showing dose- and time-dependent regulation were identified. One toxicity-associated plasma protein was identified as the cellular enzyme fumarylacetoacetate hydrolase (FAH), which is known to be required for tyrosine metabolism. The FAH gene is mutated in the human genetic disorder type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders. FAH was elevated in the plasma of animals treated with 4-AP and d-serine at early time points and returned to baseline levels after 3 weeks. The protein was not elevated in the plasma of control animals or those treated with l-serine. The presence of FAH in plasma is intriguing as it is normally a cellular enzyme with no known function in plasma. It is possible that 4-AP and d-serine may work through a previously unknown mechanism in the kidney via regulation of tyrosine metabolism or FAH activity. Therefore, FAH may function in a fashion analogous to the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes that are used to measure liver injury. The link between kidney toxicants and inherited tyrosinaemia also raises the possibility that FAH may be a marker of kidney toxicity in humans. These observations highlight the value of proteomics in identifying new biomarkers and providing new unprecedented insights into complex biological mechanisms.     

A potential biomarker of kidney damage identified by proteomics: preliminary findings

4-Aminophenol (4-AP) and d-serine are established rodent nephrotoxins that selectively damage renal proximal tubules. In an attempt to understand the mechanism of action of these toxicants in greater detail, a high throughput proteomics approach was used to profile protein changes in the plasma of animals treated with these compounds. Male Fischer 344 and Alderley Park rats were treated with increasing doses of 4-AP or d-serine and plasma samples were collected over time. Control groups received either saline or the non-toxic enantiomer, l-serine. Using high throughput two-dimensional gel analysis, a number of plasma proteins showing dose- and time-dependent regulation were identified. One toxicity-associated plasma protein was identified as the cellular enzyme fumarylacetoacetate hydrolase (FAH), which is known to be required for tyrosine metabolism. The FAH gene is mutated in the human genetic disorder type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders. FAH was elevated in the plasma of animals treated with 4-AP and d-serine at early time points and returned to baseline levels after 3 weeks. The protein was not elevated in the plasma of control animals or those treated with l-serine. The presence of FAH in plasma is intriguing as it is normally a cellular enzyme with no known function in plasma. It is possible that 4-AP and d-serine may work through a previously unknown mechanism in the kidney via regulation of tyrosine metabolism or FAH activity. Therefore, FAH may function in a fashion analogous to the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes that are used to measure liver injury. The link between kidney toxicants and inherited tyrosinaemia also raises the possibility that FAH may be a marker of kidney toxicity in humans. These observations highlight the value of proteomics in identifying new biomarkers and providing new unprecedented insights into complex biological mechanisms.     

Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.     

Identification of isocitrate dehydrogenase 1 as a potential diagnostic and prognostic biomarker for non-small cell lung cancer by proteomic analysis

Lung cancer is the leading cause of cancer-related death in the world. To explore tumor biomarkers for clinical application, two-dimensional fluorescence difference gel electrophoresis and subsequent MALDI-TOF/TOF mass spectrometry were performed to identify proteins differentially expressed in 12 pairs of lung squamous cell tumors and their corresponding normal tissues. A total of 28 nonredundant proteins were identified with significant alteration in lung tumors. The up-regulation of isocitrate dehydrogenase 1 (IDH1), superoxide dismutase 2, 14-3-3ε, and receptor of activated protein kinase C1 and the down-regulation of peroxiredoxin 2 in tumors were validated by RT-PCR and Western blot analysis in independent 15 pairs of samples. Increased IDH1 expression was further verified by the immunohistochemical study in extended 73 squamous cell carcinoma and 64 adenocarcinoma clinical samples. A correlation between IDH1 expression and poor overall survival of non-small cell lung cancer (NSCLC) patients was observed. Furthermore, ELISA analysis showed that the plasma level of IDH1 was significantly elevated in NSCLC patients compared with benign lung disease patients and healthy individuals. In addition, knockdown of IDH1 by RNA interference suppressed the proliferation of NSCLC cell line and decreased the growth of xenograft tumors in vivo. These observations suggested that IDH1, as a protein promoting tumor growth, could be used as a plasma biomarker for diagnosis and a histochemical biomarker for prognosis prediction of NSCLC.     

RAD51 as a potential biomarker and therapeutic target for pancreatic cancer

Chemotherapy is a very important therapeutic strategy for cancer treatment. The failure of conventional and molecularly targeted chemotherapeutic regimes for the treatment of pancreatic cancer highlights a desperate need for novel therapeutic interventions. Chemotherapy often fails to eliminate all tumor cells because of intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Overexpression of RAD51 protein, a key player in DNA repair/recombination has been observed in many cancer cells and its hyperexpression is implicated in drug resistance. Recent studies suggest that RAD51 overexpression contributes to the development, progression and drug resistance of pancreatic cancer cells. Here we provide a brief overview of the available pieces of evidence in support of the role of RAD51 in pancreatic tumorigenesis and drug resistance, and hypothesize that RAD51 could serve as a potential biomarker for diagnosis of pancreatic cancer. We discuss the possible involvement of RAD51 in the drug resistance associated with epithelial to mesenchymal transition and with cancer stem cells. Finally, we speculate that targeting RAD51 in pancreatic cancer cells may be a novel approach for the treatment of pancreatic cancer.     

Thioredoxin 1 as a subcellular biomarker of redox imbalance in human prostate cancer progression

We determined protein levels and subcellular distribution of thioredoxin 1 (Trx1) in human prostate tissues using tissue microarrays and analyzed redox changes in Trx1 in the nucleus and cytoplasm in cell culture models with a redox Western blot technique. We demonstrated increased nuclear Trx1 levels in high- versus low-grade human prostate cancers. Despite increased protein levels, the oxidized forms of nuclear Trx1 were higher in prostate cancer cell lines compared to their benign counterparts, suggesting that nuclear redox imbalance occurred selectively in cancer cells. A growth-stimulating dose of androgen caused transient oxidation of Trx1 in androgen-responsive prostate cancer cells only, suggesting a loss of both androgen- and redox-signaling mechanisms during cancer progression. Androgen-independent PC3 cells showed a significant increase in nuclear and cytoplasmic Trx1 protein levels, but a significant decrease in total Trx activity. Trx1 redox state and activity correlated with the sensitivity of prostate cancer cells to pro-oxidant agents, and downregulation of Trx1 sensitized cancer cells to these agents. Our findings suggest that loss of Trx function because of oxidation and corresponding redox imbalance may play important roles in prostate cancer progression and response to therapies; and Trx1 may serve as a biomarker of subcellular redox imbalance in prostate cancer.     

Thioredoxin 1 as a subcellular biomarker of redox imbalance in human prostate cancer progression

We determined protein levels and subcellular distribution of thioredoxin 1 (Trx1) in human prostate tissues using tissue microarrays and analyzed redox changes in Trx1 in the nucleus and cytoplasm in cell culture models with a redox Western blot technique. We demonstrated increased nuclear Trx1 levels in high- versus low-grade human prostate cancers. Despite increased protein levels, the oxidized forms of nuclear Trx1 were higher in prostate cancer cell lines compared to their benign counterparts, suggesting that nuclear redox imbalance occurred selectively in cancer cells. A growth-stimulating dose of androgen caused transient oxidation of Trx1 in androgen-responsive prostate cancer cells only, suggesting a loss of both androgen- and redox-signaling mechanisms during cancer progression. Androgen-independent PC3 cells showed a significant increase in nuclear and cytoplasmic Trx1 protein levels, but a significant decrease in total Trx activity. Trx1 redox state and activity correlated with the sensitivity of prostate cancer cells to pro-oxidant agents, and downregulation of Trx1 sensitized cancer cells to these agents. Our findings suggest that loss of Trx function because of oxidation and corresponding redox imbalance may play important roles in prostate cancer progression and response to therapies; and Trx1 may serve as a biomarker of subcellular redox imbalance in prostate cancer.     

A potential biomarker of kidney damage identified by proteomics: preliminary findings.

4-Aminophenol (4-AP) and D-serine are established rodent nephrotoxins that selectively damage renal proximal tubules. In an attempt to understand the mechanism of action of these toxicants in greater detail, a high throughput proteomics approach was used to profile protein changes in the plasma of animals treated with these compounds. Male Fischer 344 and Alderley Park rats were treated with increasing doses of 4-AP or D-serine and plasma samples were collected over time. Control groups received either saline or the non-toxic enantiomer, L-serine. Using high throughput two-dimensional gel analysis, a number of plasma proteins showing dose- and time-dependent regulation were identified. One toxicity-associated plasma protein was identified as the cellular enzyme fumarylacetoacetate hydrolase (FAH), which is known to be required for tyrosine metabolism. The FAH gene is mutated in the human genetic disorder type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders. FAH was elevated in the plasma of animals treated with 4-AP and D-serine at early time points and returned to baseline levels after 3 weeks. The protein was not elevated in the plasma of control animals or those treated with L-serine. The presence of FAH in plasma is intriguing as it is normally a cellular enzyme with no known function in plasma. It is possible that 4-AP and D-serine may work through a previously unknown mechanism in the kidney via regulation of tyrosine metabolism or FAH activity. Therefore, FAH may function in a fashion analogous to the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes that are used to measure liver injury. The link between kidney toxicants and inherited tyrosinaemia also raises the possibility that FAH may be a marker of kidney toxicity in humans. These observations highlight the value of proteomics in identifying new biomarkers and providing new unprecedented insights into complex biological mechanisms.     

Assessment of Ki-67 as a potential biomarker in patients with breast cancer

Breast cancer is the most common cancer in females, it accounts for one third of all malignancies affecting women. Appropriate biomarkers play significant role in predicting the prognosis and decide the specific therapy to each patient. In this study we aimed at evaluating the value of Ki-67 as a prognostic marker in breast cancer patients and to analyze the associations between Ki-67 and their clinicopathological parameters. This study included 92 patients with developed non metastatic breast cancer and 10 women had benign breast tumor served as controls. We measured the serum level by ELISA technique and tissue expression of Ki-67 by immunohistochemical technique. Our results showed that there were no statistically significant differences in serum Ki-67 levels between the two studied groups. As for Ki-67expression in breast cancer cells, the score increases with increase of tumor size, grade, premenopausal, Ki-67 expression in estrogen and progesterone receptor positive tumors showed lower values than estrogen and progesterone negative tumors, while higher Ki-67 expression was more frequently associated with HER2-positive. In conclusion; our study supports the finding that tissue Ki-67 expression may add prognostic information to that obtained from classical prognostic factors and can provide data of significant value to other important prognostic indicators such as pathological grading, and axillary lymph node involvement.     

Histidine decarboxylase is identified as a potential biomarker of intestinal mucosal injury in patients with acute intestinal obstruction

Various biomarkers currently used for the diagnosis of intestinal mucosal injury (IMI) in patients with acute intestinal obstruction have low sensitivity and specificity. In the present study, IMI, as indicated by the impaired expression of tight junction proteins, including zonula occludens-1, occludin and claudin-1, and inflammation were determined in colonic tissues of patients with 45 strangulated intestinal obstruction (STR-IO) and the adjacent "normal" colonic tissues of 35 patients with colon cancers by quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting, immunohistochemistry and histological examination, respectively. Then, two-dimensional fluorescent difference gel electrophoresis coupled with linear trap quadrupole mass spectrometry was used to screen for potential biomarkers of IMI in the serum samples of 10 STR-IO, 10 simple intestinal obstruction (SIM-IO) and 10 normal healthy controls. A total of 35 protein spots were differentially expressed among the serum samples, and six of the proteins were identified as potential biomarkers. Among the six proteins, histidine decarboxylase (HDC) and ceruloplasmin (CP) were elevated significantly in patients with STR-IO, compared with patients with SIM-IO and healthy controls. Thus, HDC and CP were further validated by QRT-PCR, Western blotting, immunohistochemistry and enzyme-linked immunosorbent assay, respectively, in colonic tissues, serum and urine samples. Finally, the receiver operating characteristic curves were used to show the area under the curves of HDC, CP and several established biomarkers, followed by the determination of the appropriate cutoff values and their sensitivities and specificities. It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of IMI in patients with acute intestinal obstruction, although further validation in a larger cohort is required.     

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.     

Proteomics in prostate cancer biomarker discovery

Despite advances in molecular medicine, genomics, proteomics and translational research, prostate cancer remains the second most common cause of cancer-related mortality for men in the Western world. Clearly, early detection, targeted treatment and post-treatment monitoring are vital tools to combat this disease. Tumor markers can be useful for diagnosis and early detection of cancer, assessment of prognosis, prediction of therapeutic effect and treatment monitoring. Such tumor markers include prostate-specific antigen (prostate), cancer antigen (CA)15.3 (breast), CA125 (ovarian), CA19.9 (gastrointestinal) and serum α-fetoprotein (testicular cancer). However, all of these biomarkers lack sensitivity and specificity and, therefore, there is a large drive towards proteomic biomarker discovery. Current research efforts are directed towards discovering biosignatures from biological samples using novel proteomic technologies that provide high-throughput, in-depth analysis and quantification of the proteome. Several of these studies have revealed promising biomarkers for use in diagnosis, assessment of prognosis, and targeting treatment of prostate cancer. This review focuses on prostate cancer proteomic biomarker discovery and its future potential.