Pancreatic Cancer Biomarkers
Representative Biomarkers Full List of Biomarkers Tested Data-Supported Products
Pancreatic cancer, a malignancy originating from the pancreatic ductal epithelium, represents one of the most lethal forms of cancer, with a 5-year survival rate that remains dismally low. This dire prognosis is largely due to the disease's asymptomatic nature in its early stages, leading to late diagnosis in the majority of cases. The pancreas, a vital organ located behind the stomach, plays a crucial role in digestion and metabolism, secreting enzymes that aid digestion and hormones such as insulin that regulate blood sugar. Pancreatic cancer is notoriously resistant to conventional treatments, including surgery, chemotherapy, and radiation therapy, partly because of its ability to evade detection until it has progressed to an advanced stage. Additionally, its complex tumor microenvironment and the presence of dense stromal tissue around the cancer cells further complicate treatment efforts. Recent research efforts are focused on understanding the genetic and molecular underpinnings of the disease, with the hope of developing targeted therapies that can improve patient outcomes. Despite these challenges, advances in diagnostic imaging, minimally invasive surgical techniques, and the exploration of new treatment modalities offer a glimmer of hope for those affected by this devastating disease.
Figure 1 Biomarker candidates for the diagnosis of pancreatic cancer. (Wu, 2022)
Representative Biomarkers of Pancreatic Cancer
PSCA
The Prostate Stem Cell Antigen (PSCA) is a cell surface glycoprotein initially identified in prostate cancer but is also expressed in several other types of cancers, including pancreatic cancer. Structurally, PSCA is a member of the Thy-1/Ly-6 family, which is known for its roles in cell adhesion and signaling. In pancreatic cancer, PSCA plays a multifaceted role, contributing to the disease's progression, metastasis, and resistance to therapy. Its expression is upregulated in pancreatic cancer tissues compared to normal pancreatic tissues, making it a potential biomarker for diagnosis and prognosis. Functionally, PSCA's role in pancreatic cancer involves promoting cell proliferation, inhibiting apoptosis (cell death), and enhancing cell migration and invasion, thereby facilitating tumor growth and spread. Additionally, PSCA may influence the tumor microenvironment to favor cancer progression, including immune evasion mechanisms. Given its significant role in pancreatic cancer biology, PSCA is also being explored as a target for therapeutic interventions, with strategies including monoclonal antibodies and vaccine approaches aimed at reducing tumor growth and improving patient outcomes.
Recommended Mouse Anti-PSCA mAb (CAT#: HPAB-0287CQ)
Figure 2 ELISA analysis of HPAB-0287CQ was performed by coating with Human PSCA Protein, His Tag. The secondary antibody: HRP-Anti-Mouse IgG (H+L)
MUC1
MUC1, short for Mucin 1, is a transmembrane glycoprotein expressed on the apical surface of epithelial cells, playing a crucial role in protecting and lubricating the cell surface. In the context of pancreatic cancer, MUC1 is overexpressed and undergoes aberrant glycosylation, leading to a disruption in normal cell signaling pathways. This overexpression is associated with cancer progression, metastasis, and resistance to chemotherapy. MUC1 promotes tumor growth and metastasis by enhancing cell proliferation, survival, and invasion through its interaction with various signaling molecules and pathways, including the PI3K/Akt and NF-κB pathways. Additionally, MUC1's altered glycosylation patterns in pancreatic cancer can shield tumor cells from immune surveillance, contributing to immune evasion. Moreover, the detection of MUC1 expression levels and its antibodies in serum has been explored as a biomarker for the diagnosis and prognosis of pancreatic cancer, reflecting its significant role in the disease's pathology.
Recommended Humanized Anti-MUC1 mAb (Gatipotuzumab) (CAT#: TAB-026ML)
Figure 3 The purity of TAB-026ML was greater than 95% as determined by SEC-HPLC.
Recommended Mouse Anti-MUC1 mAb (CAT#: ZG-0016C)
Figure 4 Immunohistochemical analysis of paraffin-embedded Tonsil. 1, Antibody was diluted at 1:200 (4° overnight). 2, TRIS-EDTA of pH 8.0 was used forantigen retrieval. 3, Secondary antibody was diluted at 1:200 (room temperature, 30 min).
Recommended Rabbit Anti-MUC1 mAb (CAT#: ZG-0352U)
Figure 5 Epithelial membrane antigen expression in pulmonary adenocarcinoma, stained with anti-CD227 antibody. Formalin fixed, paraffin embedded human tissues (4 μm sections) stained.
MDM2
MDM2 (Mouse Double Minute 2 homolog) is a critical oncogene that plays a pivotal role in cellular proliferation and apoptosis, acting primarily through its interaction with the tumor suppressor protein p53. In the context of pancreatic cancer, a disease characterized by aggressive behavior and poor prognosis, MDM2 assumes a crucial oncogenic role by inhibiting the tumor suppressor functions of p53. This interaction is significant as p53 is responsible for initiating cell cycle arrest and apoptosis in response to DNA damage or oncogenic stress, mechanisms central to the prevention of cancer development. Overexpression of MDM2 in pancreatic cancer leads to decreased p53 activity, facilitating unchecked cellular division, survival, and tumorigenesis. Furthermore, the MDM2-p53 axis is a focal point for the development of targeted therapies aimed at reactivating p53 function, offering hope for improved treatment options for pancreatic cancer patients. The modulation of MDM2 levels or disrupting its interaction with p53 presents a promising therapeutic strategy, potentially restoring the apoptotic capability of cancer cells and inhibiting tumor progression.
Recommended Rabbit Anti-MDM2 mAb (CAT#: ZG-0396U)
Figure 6 Immunohistochemical staining patterns of formalin fixed and paraffin embedded human liposarcoma tissue (4 μm sections) with Anti - mdm2 antibody using Ventana BenchMark. The liposarcoma tissues show strong nuclear mdm2 expression.
Full List of Pancreatic Cancer Biomarkers
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| BRAF | B-Raf Proto-Oncogene, Serine/Threonine Kinase; V-Raf Murine Sarcoma Viral Oncogene Homolog B1; V-Raf Murine Sarcoma Viral Oncogene Homolog B; Proto-Oncogene B-Raf; BRAF1; RAFB1; B-Raf Proto-Oncogene Serine/Threonine-Protein Kinase (P94); Murine Sarcoma Viral (V-Raf) Oncogene Homolog B1; Serine/Threonine-Protein Kinase B-Raf | 673 | P15056 | This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. |
| CDKN2A | Cyclin Dependent Kinase Inhibitor 2A; Cyclin-Dependent Kinase Inhibitor 2A (Melanoma, P16, Inhibits CDK4); Cyclin-Dependent Kinase 4 Inhibitor A; Cyclin-Dependent Kinase Inhibitor 2A; Multiple Tumor Suppressor 1; Alternative Reading Frame; P16-INK4A; P16INK4A; P14ARF; CDKN2; CDK4I; MTS-1; MTS1; MLM | 1029 | P42771 | CDKN2A loss has been shown to be a significant event in a number of cancer types. While no targeted therapeutic has been engaged in clinical trials, the prognostic impact has been studied by a number of meta-analyses. In majority of cases CDKN2A is inactivated by homozygous deletions. One of the mechanisms by which loss of CDKN2A can occur is by hypermethylation of the promoter region for the gene. |
| CEACAM1 | CEACAM1; carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein); BGP; BGP1; BGPI; carcinoembryonic antigen-related cell adhesion molecule 1; antigen CD66; CD66a antigen | 634 | P13688 | This gene encodes a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily. Two subgroups of the CEA family, the CEA cell adhesion molecules and the pregnancy-specific glycoproteins, are located within a 1.2 Mb cluster on the long arm of chromosome 19. Eleven pseudogenes of the CEA cell adhesion molecule subgroup are also found in the cluster. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Subsequently, it was found to be a cell-cell adhesion molecule detected on leukocytes, epithelia, and endothelia. The encoded protein mediates cell adhesion via homophilic as well as heterophilic binding to other proteins of the subgroup. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature of all variants has not been defined. |
| EGFR | Epidermal Growth Factor Receptor; Receptor Tyrosine-Protein Kinase ErbB-1; Erb-B2 Receptor Tyrosine Kinase 1; Proto-Oncogene C-ErbB-1; EC 2.7.10.1; ERBB1; ERBB; HER1; Epidermal Growth Factor Receptor (Avian Erythroblastic Leukemia Viral (V-Erb-B) Oncogene Homolog); Erythroblastic Leukemia Viral (V-Erb-B) Oncogene Homolog (Avian) | 1956 | P00533 | The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jun 2016] |
| HER2 | NEU; NGL; HER2; TKR1; CD340; HER-2; MLN 19; HER-2/neu | 2064 | P04626 | This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. |
| KRAS | NS; NS3; CFC2; RALD; K-Ras; KRAS1; KRAS2; RASK2; KI-RAS; C-K-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; c-Ki-ras2 | 3845 | P01116 | This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008] |
| MDM2 | MDM2 Proto-Oncogene; MDM2 Proto-Oncogene, E3 Ubiquitin Protein Ligase; Oncoprotein Mdm2; Hdm2; Mdm2, Transformed 3T3 Cell Double Minute 2, P53 Binding Protein (Mouse); Mdm2, Transformed 3T3 Cell Double Minute 2, P53 Binding Protein; Mouse Double Minute 2, Human Homolog Of; P53-Binding Protein; Double Minute 2, Human Homolog Of; P53-Binding Protein; Mdm2, P53 E3 Ubiquitin Protein Ligase Homolog; MDM2 Oncogene, E3 Ubiquitin Protein Ligase | 4193 | A7UKX8 | This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013] |
| MSH2 | MutS Homolog 2; HMSH2; MutS (E. Coli) Homolog 2 (Colon Cancer, Nonpolyposis Type 1); MutS Homolog 2, Colon Cancer, Nonpolyposis Type 1 (E. Coli); MutS Homolog 2, Colon Cancer, Nonpolyposis Type 1; DNA Mismatch Repair Protein Msh2; MutS Protein Homolog 2 | 4436 | P43246 | This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. Coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012] |
| MUC1 | ADMCKD; ADMCKD1; CA 15-3; CD227; EMA; H23AG; KL-6; MAM6; MCD; MCKD; MCKD1; MUC-1; MUC-1/SEC; MUC-1/X; MUC1/ZD; PEM; PEMT; PUM | 4582 | P15941 | This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants. |
| MUC4 | Mucin 4, Cell Surface Associated; Pancreatic Adenocarcinoma Mucin; Mucin 4, Tracheobronchial; Ascites Sialoglycoprotein; Tracheobronchial Mucin; Testis Mucin | 4585 | Q99102 | The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008] |
| p53 | 7157 | K7PPA8 | ||
| PNLIPRP1 | PNLIPRP1; pancreatic lipase-related protein 1; PLRP1; Pancreatic lipase related protein 1; PLRP1; PL-RP1; OTTHUMP00000020567; OTTHUMP00000230058; OTTHUMP00000230064; | 5407 | P54315 | |
| PRSS2 | TRY2; TRY8; TRYP2 | 5645 | P07478 | This gene belongs to the trypsin family of serine proteases and encodes anionic trypsinogen. It is part of a cluster of trypsinogen genes that are located within the T cell receptor beta locus. Enzymes of this family cleave peptide bonds that follow lysine or arginine residues. This protein is found at high levels in pancreatic juice and its upregulation is a characteristic feature of pancreatitis. This protein has also been found to activate pro-urokinase in ovarian tumors, suggesting a function in tumor invasion. In addition, this enzyme is able to cleave across the type II collagen triple helix in rheumatoid arthritis synovitis tissue, potentially participating in the degradation of type II collagen-rich cartilage matrix. Alternative splicing results in multiple transcript variants. |
| 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. |
| Ron | CD136; CDw136; NPCA3; PTK8; RON | 4486 | Q04912 | Macrophage stimulating 1 receptor (MST1R) is a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. |
| STK11 | PJS; LKB1; hLKB1 | 6794 | Q15831 | The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. |
Tested Data-Supported Products Targeting Pancreatic Cancer Biomarkers
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Reference
- Wu, Haotian, et al. "Advances in biomarkers and techniques for pancreatic cancer diagnosis." Cancer Cell International 22.1 (2022): 1-12.
For research use only. Not intended for any clinical use.
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