Prostate Cancer Biomarkers
Representative Biomarkers Full List of Biomarkers Tested Data-Supported Products
Prostate cancer is a significant health concern affecting men worldwide, marked by its high mortality rates, particularly in Western countries. It predominantly targets middle-aged men between 45 to 60 years old. The diagnosis of prostate cancer involves a combination of procedures including prostate biopsies, prostate-specific antigen (PSA) testing, digital rectal examination, and magnetic resonance imaging (MRI). Key risk factors for prostate cancer encompass family history, ethnicity, age, obesity, and other environmental factors. Prostate cancer's heterogeneity in epidemiology and genetics is influenced by a mix of genetic, environmental, and social factors, leading to race-specific survival rate discrepancies. There is strong evidence supporting the genetic contribution to prostate cancer risk, particularly through family inheritance. Research has also highlighted the role of genetic variations in androgen biosynthesis and metabolism in the disease's onset and progression. Current treatments vary based on the cancer's nature and may include active surveillance, chemotherapy, radiation therapy, hormonal therapy, surgery, and cryotherapy, each associated with its own set of potential side effects. Ongoing research is directed towards finding more effective and less harmful treatment options, including traditional medicine, nanotechnologies, and gene therapy.
Figure 1 A schematic depicting the development of prostate cancer. (Sekhoacha, 2022)
Representative Biomarkers of Prostate Cancer
PSMA
Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly expressed in prostate epithelial cells and is significantly upregulated in prostate cancer, making it a critical biomarker for this disease. Functionally, PSMA has folate hydrolase and neuropeptidase activities, playing roles in nutrient acquisition and signal transduction within the prostate tissue. Its overexpression in prostate cancer, especially in higher-grade tumors, metastatic sites, and castration-resistant prostate cancer (CRPC), has made PSMA a prominent target for diagnostic imaging and therapeutic approaches. PSMA-targeted imaging agents, such as PSMA-PET scans, have shown high sensitivity and specificity in detecting prostate cancer lesions, improving the accuracy of staging and restaging. Therapeutically, PSMA provides a target for radioligand therapy and antibody-drug conjugates, which deliver cytotoxic agents directly to cancer cells, sparing normal tissues and reducing side effects. The development of PSMA-targeted therapies has opened new avenues for precision medicine in prostate cancer, offering hope for improved outcomes in patients with advanced disease.
Recommended Mouse Anti-PSMA mAb (CAT#: ZG-0950F)
Figure 2 Indirect immunofluorescence staining of PSMA in the prostate cancer cell line LNCaP cells using anti-PSMA antibody (clone 107.1A4) (diluted 1:500). Note the membranous localization of PSMA. Nuclear DNA staining with DAPI.
AMACR
Alpha-methylacyl-CoA racemase (AMACR) is a key enzyme involved in the beta-oxidation of branched-chain fatty acids and bile acid intermediates, playing a crucial role in lipid metabolism. Within the context of prostate cancer, AMACR has gained prominence due to its significantly elevated expression levels in cancerous prostate cells compared to normal prostate tissue. This overexpression of AMACR has been leveraged as a diagnostic marker for prostate cancer, aiding in the histopathological differentiation of cancerous lesions from benign prostatic hyperplasia and normal prostate tissue. The precise mechanisms through which AMACR contributes to prostate carcinogenesis are not fully elucidated but are thought to involve alterations in fatty acid metabolism that may support the rapid growth and proliferation of cancer cells. Furthermore, the role of AMACR in prostate cancer extends beyond its diagnostic utility; it is also being explored as a potential therapeutic target. By inhibiting AMACR activity, researchers aim to disrupt the metabolic pathways critical for tumor growth and survival, offering a novel approach to prostate cancer treatment.
Recommended Mouse Anti-AMACR mAb (CAT#: HPAB-0570-YJ)
Figure 3 Immunofluorescence analysis of Rat-brain tissue. 1.AMACR Monoclonal Antibody (red) was diluted at 1:200 (4°C, overnight). 2, Cy3 labled Secondary Antibody was diluted at 1:300 (room temperature, 50min).3, Picture B: DAPI(blue) 10min. Picture A:Target. Picture B: DAPI. Picture C:merge of A+B.
Recommended Mouse Anti-AMACR mAb (CAT#: ZG-0283F)
Figure 4 Immunohistochemical analysis of paraffin-embedded human normal prostate tissue (left) and prostate adenocarcinoma tissue (right), showing the cytoplasmic localization of DAB staining with AMACR monoclonal antibody.
Recommended Mouse Anti-AMACR mAb (CAT#: ZG-0025J)
Figure 5 Immunohistochemical analysis of paraffin-embedded Prostatic carcinoma. 1. Antibody was diluted at 1:200 (4°C overnight). 2, TRIS-EDTA of pH8.0 was used for antigen retrieval. 3, Secondary Antibody was diluted at 1:200 (room temperature, 30min).
TGFB1
TGFB1 (Transforming Growth Factor Beta 1) is a multifunctional cytokine belonging to the transforming growth factor beta superfamily, which regulates a wide range of cellular processes including cell growth, differentiation, apoptosis, cellular homeostasis, and other physiological functions. In prostate cancer, TGFB1 plays a dual role, acting as a tumor suppressor in early stages of tumor development by inhibiting cell proliferation and promoting apoptosis, but later facilitating tumor progression and metastasis in advanced stages of the disease. The switch from a tumor suppressor to a tumor promoter involves complex interactions within the tumor microenvironment, influencing cancer cell migration, invasion, and evasion of immune surveillance. Additionally, TGFB1 is implicated in promoting the epithelial-to-mesenchymal transition (EMT), a critical event in cancer metastasis, where cancer cells gain migratory and invasive capabilities. The expression and signaling pathways of TGFB1 are intricately regulated and can be influenced by genetic and epigenetic modifications within prostate cancer cells, making it a significant focus for understanding cancer progression mechanisms and developing potential therapeutic interventions.
Recommended Mouse Anti-TGFB1 mAb (CAT#: ZG-0116C)
Figure 6 Immunohistochemical analysis of paraffin-embedded Human Breast Carcinoma Tissue using TGFβ1 Mouse mAb diluted at 1:200.
Recommended Mouse Anti-TGFB1 mAb (CAT#: ZG-0117C)
Figure 7 Immunohistochemical analysis of paraffin-embedded Rat Brain Tissue using TGFβ1 Mouse mAb diluted at 1:200.
Full List of Prostate Cancer Biomarkers
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| AKR1C3 | DD3; DDX; PGFS; HAKRB; HAKRe; HA1753; HSD17B5; hluPGFS; aldo-keto reductase family 1 member C3; 3-alpha hydroxysteroid dehydrogenase, type II; 3-alpha-HSD type II, brain; chlordecone reductase homolog HAKRb; dihydrodiol dehydrogenase 3; dihydrodiol dehydrogenase X; indanol dehydrogenase; prostaglandin F synthase; testosterone 17-beta-dehydrogenase 5; trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; type IIb 3-alpha hydroxysteroid dehydrogenase | 8644 | P42330 | Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone. |
| AMACR | Alpha-Methylacyl-CoA Racemase; 2-Methylacyl-CoA Racemase; EC 5.1.99.4; AMACRD; CBAS4; P504S; RACE; RM; | 23600 | Q9UHK6 | This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. |
| AZGP1 | AZGP1; Alpha-2-Glycoprotein, Zinc; Zn-Alpha-2-GP; Zinc-Alpha-2-Glycoprotein; Alpha-2-Glycoprotein 1, Zinc-Binding; ZAG; Zn-Alpha2-Glycoprotein; Alpha-2-Glycoprotein 1, Zinc; ZA2G; Zn-Alpha-2-Glycoprotein; ZNGP1 | 563 | P25311 | Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids |
| CD147 | Gavilimomab; 244096-20-6; ABX-CBL; ABX-CBL; BSG; basigin (Ok blood group); basigin (OK blood group), OK; basigin | 682 | P35613 | The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. |
| EZH2 | WVS; ENX1; KMT6; WVS2; ENX-1; EZH2b; KMT6A; EZH2 | 2146 | Q15910 | This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. |
| HPN | TMPRSS1 | 3249 | P05981 | This gene encodes a type II transmembrane serine protease that may be involved in diverse cellular functions, including blood coagulation and the maintenance of cell morphology. Expression of the encoded protein is associated with the growth and progression of cancers, particularly prostate cancer. The protein is cleaved into a catalytic serine protease chain and a non-catalytic scavenger receptor cysteine-rich chain, which associate via a single disulfide bond. Alternative splicing results in multiple transcript variants. |
| IL6 | Interleukin 6# | 3569 | P05231 | This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015] |
| KLK2 | hK2; hGK-1; KLK2A2; kallikrein-2; glandular kallikrein 2 glandular kallikrein-1 kallikrein 2, prostatic tissue kallikrein-2 | 3817 | P20151 | This gene encodes a member of the grandular kallikrein protein family. Kallikreins are a subgroup of serine proteases that are clustered on chromosome 19. Members of this family are involved in a diverse array of biological functions. The protein encoded by this gene is a highly active trypsin-like serine protease that selectively cleaves at arginine residues. This protein is primarily expressed in prostatic tissue and is responsible for cleaving pro-prostate-specific antigen into its enzymatically active form. This gene is highly expressed in prostate tumor cells and may be a prognostic maker for prostate cancer risk. |
| MSMB | MSMB; PSP-94; Prostate Secreted Seminal Plasma Protein; Prostate Secretory Protein Of 94 Amino Acids; MSP; PSP; HPC13; Seminal Plasma Beta-Inhibin; PN44; PSP94; Immunoglobulin Binding Factor; Prsp; IGBF; PRPS; Microseminoprotein, Beta-; MSPB; PSP57; Beta- | 4477 | P08118 | The protein encoded by this gene is a member of the immunoglobulin binding factor family. It is synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. This protein has inhibin-like activity. It may have a role as an autocrine paracrine factor in uterine, breast and other female reproductive tissues. The expression of the encoded protein is found to be decreased in prostate cancer. Two alternatively spliced transcript variants encoding different isoforms are described for this gene. The use of alternate polyadenylation sites has been found for this gene. |
| Nucb2 | Nesfatin-1 | 4925 | P80303 | Nesfatin-1 is a neuropeptide produced in the hypothalamus of mammals. It participates in the regulation of hunger and fat storage. Increased nesfatin-1 in the hypothalamus contributes to diminished hunger, a 'sense of fullness', and a potential loss of body fat and weight. |
| PSA | Psa | 354 | P07288 | |
| PSAP | GLBA; SAP1; SAP2; PSAPD; PARK24 | 5660 | P07602 | This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. |
| PSCA | PSCA; UNQ206; PRO232 | 8000 | O43653 | This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas. This gene includes a polymorphism that results in an upstream start codon in some individuals; this polymorphism is thought to be associated with a risk for certain gastric and bladder cancers. Alternative splicing results in multiple transcript variants. |
| PSMA | Prostate-specific membrane antigen; PSMA | 2346 | Q04609 | The new prostate-specific membrane antigen (PSMA) PET imaging will significantly improve the detection and treatment of prostate cancer. The FDA approved the drug for positron emission tomography (PET) imaging of PSMA-positive lesions in men with prostate cancer. 68Ga-PSMA-11 is a radioactive imaging agent that binds to prostate cancer cells to help locate prostate cancer cells. |
| STEAP1 | STEAP; PRSS24; STEAP1; STEAP family member 1 | 26872 | Q9UHE8 | This gene is predominantly expressed in prostate tissue, and is found to be upregulated in multiple cancer cell lines. The gene product is predicted to be a six-transmembrane protein, and was shown to be a cell surface antigen significantly expressed at cell-cell junctions. |
| Tgfb1 | TGF beta 1; TGFβ1 | 21803 | P28907 | TGFβ1 is a cytokine, whose full name is Transforming Growth Factor Beta 1. It is a protein that regulates cell proliferation, differentiation, and embryonic development, and also plays an important role in immune regulation, inflammatory responses, and tumor development. |
| TMEFF2 | TR; HPP1; TPEF; TR-2; TENB2; CT120.2 | 23671 | Q9UIK5 | This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. |
| uPA | ATF; BDPLT5; QPD; u-PA; UPA; URK | 5328 | P00749 | This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimers disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. |
Tested Data-Supported Products Targeting Prostate Cancer Biomarkers
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Reference
- Sekhoacha, Mamello, et al. "Prostate cancer review: Genetics, diagnosis, treatment options, and alternative approaches." Molecules 27.17 (2022): 5730.
For research use only. Not intended for any clinical use.
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