The footprints of cancer development: Cancer biomarkers.

Diagnostic detection and measurement of cancer disease progression are essential elements for successful cancer disease management. The early stages of cancer development carry the maximum potential for therapeutic interventions. However, these stages are often asymptomatic, leading to delayed diagnosis at the very advanced stages when effective treatments are unavailing. The application of biomarkers to cancer is leading the way because of the unique association of genomic changes in cancer cells with the disease process. They have the potential to not only help identify who will develop cancer but also to predict as to when the event is most likely to occur. In recent years, there has been an enormous effort to develop specific and sensitive biomarkers for precise and accurate screening, diagnosis, prognosis and monitoring of high risk cancer to assist with therapeutic decisions. The present article is a brief review of the emerging trends in the development of biomarkers for early detection and precise evaluation of cancer disease.

[1]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[2]  T. Wheeler,et al.  A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. , 2000, Cancer research.

[3]  E. Andreu,et al.  The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3–4, is downregulated by hypermethylation in acute lymphoblastic leukemia , 2004, Leukemia.

[4]  A. Jemal,et al.  Cancer Statistics, 2004 , 2004, CA: a cancer journal for clinicians.

[5]  Izabela Berdowska,et al.  Cysteine proteases as disease markers. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[6]  J. Kos,et al.  Cysteine proteinases in cancer progression and their clinical relevance for prognosis. , 1998, Biological chemistry.

[7]  J. S. Rao,et al.  Molecular mechanisms of glioma invasiveness: the role of proteases , 2003, Nature Reviews Cancer.

[8]  M. Hoque,et al.  Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  E. Diamandis,et al.  Human tissue kallikreins: physiologic roles and applications in cancer. , 2004, Molecular cancer research : MCR.

[10]  T. Godfrey,et al.  Quantitative analysis of circulating plasma DNA as a tumor marker in thoracic malignancies. , 2005, Clinical chemistry.

[11]  T. Caputo,et al.  Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers. , 2000, American journal of obstetrics and gynecology.

[12]  G. Kristiansen,et al.  Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues , 2003, The Prostate.

[13]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Bonnie F. Sloane,et al.  Unraveling the role of proteases in cancer. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[15]  R. DiPaola,et al.  Extracellular catalytic subunit activity of the cAMP-dependent protein kinase in prostate cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  E. Lander,et al.  Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Montenarh Humoral Immune Response Against the Growth Suppressor p53 in Human Malignancies , 2000 .

[18]  Z. Zhang,et al.  Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL. , 2000, Urology.

[19]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[20]  A. Stromberg,et al.  Profiling Tumor-Associated Antibodies for Early Detection of Non-small Cell Lung Cancer , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[21]  L. Bégin,et al.  Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection. , 2002, Urology.

[22]  Sudhir Srivastava,et al.  Nanotechnology in Early Detection of Cancer , 2002, Laboratory Investigation.

[23]  George A. Calin,et al.  MicroRNA-Cancer Connection: The Beginning of a New Tale , 2008 .

[24]  W. Isaacs,et al.  DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. , 1999, Cancer research.

[25]  Debashis Ghosh,et al.  Humoral Immune Response to α-Methylacyl-CoA Racemase and Prostate Cancer , 2004 .

[26]  R. Gertz,et al.  The significance of urokinase‐type plasminogen activator, its inhibitors, and its receptor in ascites of patients with epithelial ovarian cancer , 1995, Cancer.

[27]  S. Kingsmore Multiplexed protein measurement: technologies and applications of protein and antibody arrays , 2006, Nature Reviews Drug Discovery.

[28]  W. Cho,et al.  Contribution of oncoproteomics to cancer biomarker discovery , 2007, Molecular Cancer.

[29]  K. Jain,et al.  Applications of nanobiotechnology in clinical diagnostics. , 2007, Clinical chemistry.

[30]  A. Blejec,et al.  Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients. , 2002, Cancer detection and prevention.

[31]  O. Vorm,et al.  Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. , 2001, Cancer research.

[32]  J. Herman Circulating Methylated DNA , 2004, Annals of the New York Academy of Sciences.

[33]  D. Morton,et al.  Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  H. Klocker,et al.  Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis. , 2003, Urology.

[35]  Bonnie F. Sloane,et al.  Cysteine cathepsins in human cancer , 2004, Biological chemistry.

[36]  D. Wazer,et al.  Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression. , 1996, Cancer research.

[37]  J. Joyce,et al.  Cysteine cathepsin proteases as pharmacological targets in cancer. , 2008, Trends in pharmacological sciences.

[38]  Jose M. Silva,et al.  Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations. , 1999, Cancer research.

[39]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[40]  P. VandeVord,et al.  Autoimmunity to the Mr 32,000 subunit of replication protein A in breast cancer , 2002 .

[41]  H. Levin,et al.  Preoperative PSA is still predictive of cancer volume and grade in late PSA era. , 2007, Urology.

[42]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[43]  Bob Djavan,et al.  Prostate cancer screening markers , 2007 .

[44]  J. Wolfe,et al.  Expression of the plasminogen activation system in kidney cancer correlates with its aggressive phenotype. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[45]  A. Jemal,et al.  Cancer Statistics, 2007 , 2007, CA: a cancer journal for clinicians.

[46]  D. Hanahan,et al.  Multiple Roles for Cysteine Cathepsins in Cancer , 2004, Cell cycle.

[47]  Nan Hu,et al.  2D Differential In-gel Electrophoresis for the Identification of Esophageal Scans Cell Cancer-specific Protein Markers* , 2002, Molecular & Cellular Proteomics.

[48]  R. Uzzo,et al.  Detection of Bladder Cancer in Urine by a Tumor Suppressor Gene Hypermethylation Panel , 2004, Clinical Cancer Research.

[49]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[50]  T. Okanoue,et al.  Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues , 2006, Oncogene.

[51]  R. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer , 2007, Nature.

[52]  Jerome P. Richie,et al.  Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. , 1998, JAMA.

[53]  G. Maira,et al.  Extensive modulation of a set of microRNAs in primary glioblastoma. , 2005, Biochemical and biophysical research communications.

[54]  C. Moon,et al.  Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer , 2004, Clinical Cancer Research.

[55]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[56]  D. Brömme,et al.  Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. , 2002, Current pharmaceutical design.

[57]  Cancer Proteomics: New Developments in Clinical Chemistry. Krebs-„Proteomics": Neue Entwicklungen in der klinischen Chemie , 2001 .

[58]  E. Metter,et al.  Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging. , 2001, Urology.

[59]  D. Katsaros,et al.  Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies. , 2001, Cancer research.

[60]  William C Reinhold,et al.  Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[61]  D. Ornstein,et al.  Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. , 1997, JAMA.

[62]  K. Jung,et al.  Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue , 2001, British Journal of Cancer.

[63]  Bela Molnar,et al.  DNA methylation biomarkers for blood-based colorectal cancer screening. , 2008, Clinical chemistry.

[64]  Andrew J Vickers,et al.  The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically‐based screening strategy , 2007, International journal of cancer.

[65]  P. Choong,et al.  The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[66]  David E. Misek,et al.  Integral Protein Microarrays for the Identification of Lung Cancer Antigens in Sera That Induce a Humoral Immune Response*S , 2008, Molecular & Cellular Proteomics.

[67]  G. Yousef,et al.  KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer. , 2000, Genomics.

[68]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.

[69]  Miltiadis Paliouras,et al.  Human tissue kallikreins: the cancer biomarker family. , 2007, Cancer letters.

[70]  H. Klocker,et al.  Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml. , 2003, The Journal of urology.

[71]  Aamir Ahmad,et al.  Evolving role of uPA/uPAR system in human cancers. , 2008, Cancer treatment reviews.

[72]  D. Hanahan,et al.  Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. , 2004, Cancer cell.

[73]  Andrew J Vickers,et al.  Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  R. Aharonov,et al.  MicroRNAs accurately identify cancer tissue origin , 2008, Nature Biotechnology.

[75]  J. Trent,et al.  α-methylacyl-CoA racemase: A new molecular marker for prostate cancer , 2002 .

[76]  D. Tindall,et al.  Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis. , 1999, Urology.

[77]  Kim-Anh Do,et al.  Fingerprinting the circulating repertoire of antibodies from cancer patients , 2003, Nature Biotechnology.

[78]  D. Chan,et al.  Use of percentage of free prostate-specific antigen to identify men at high risk of prostate cancer when PSA levels are 2.51 to 4 ng/mL and digital rectal examination is not suspicious for prostate cancer: an alternative model. , 1999, Urology.

[79]  G. Yousef,et al.  Identification and molecular characterization of five novel kallikrein gene 13 (KLK13; KLK-L4) splice variants: differential expression in the human testis and testicular cancer. , 2001, Anticancer Research.

[80]  Martin Widschwendter,et al.  Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. , 2005, Cancer research.

[81]  Gary Ruvkun,et al.  Glimpses of a Tiny RNA World , 2001, Science.

[82]  S. Nie,et al.  Nanotechnology applications in cancer. , 2007, Annual review of biomedical engineering.

[83]  E Gabrielson,et al.  Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Stephen D Mikolajczyk,et al.  Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. , 2003, The Keio journal of medicine.

[85]  Hedi Mattoussi,et al.  Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy , 2004, Nature Medicine.

[86]  Neil D. Rawlings,et al.  MEROPS: the peptidase database , 2009, Nucleic Acids Res..

[87]  K. Jain,et al.  Recent advances in clinical oncoproteomics. , 2007, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[88]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[89]  J. Herman,et al.  Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. , 2000, Cancer research.

[90]  A. Jemal,et al.  Cancer Statistics, 2005 , 2005, CA: a cancer journal for clinicians.

[91]  Debashis Ghosh,et al.  Autoantibody signatures in prostate cancer. , 2005, The New England journal of medicine.

[92]  J. Jett,et al.  Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[93]  H. Hibshoosh,et al.  Isolation of native human monoclonal autoantibodies to breast cancer. , 2002, Hybridoma and hybridomics.

[94]  E. Krebs,et al.  Phosphorylation-dephosphorylation of enzymes. , 1979, Annual review of biochemistry.

[95]  T. Stamey,et al.  Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter. , 2002, Urology.

[96]  S. Shetty,et al.  Urokinase receptor in human malignant mesothelioma cells: role in tumor cell mitogenesis and proteolysis. , 1995, The American journal of physiology.

[97]  N. Dubin,et al.  Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[98]  B. Turk Targeting proteases: successes, failures and future prospects , 2006, Nature Reviews Drug Discovery.

[99]  J. Kos,et al.  Cysteine Proteinases and Their Inhibitors in Extracellular Fluids: Markers for Diagnosis and Prognosis in Cancer , 2000, The International journal of biological markers.

[100]  G. Yousef,et al.  Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues* , 2000, The Journal of Biological Chemistry.

[101]  H. Horvitz,et al.  Heterochronic mutants of the nematode Caenorhabditis elegans. , 1984, Science.

[102]  W. Gerald,et al.  Endogenous human microRNAs that suppress breast cancer metastasis , 2008, Nature.

[103]  Peter A. Jones,et al.  Cancer-epigenetics comes of age , 1999, Nature Genetics.

[104]  E. Fung,et al.  Proteomic approaches to tumor marker discovery. , 2002, Archives of pathology & laboratory medicine.

[105]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[106]  C. Lucchinetti,et al.  Anti‐neuronal nuclear autoantibody type 2: Paraneoplastic accompaniments , 2003, Annals of neurology.

[107]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[108]  S. Memarzadeh,et al.  Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[109]  C. Croce,et al.  MicroRNA expression and function in cancer. , 2006, Trends in molecular medicine.

[110]  W. Catalona,et al.  Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. , 2006, Urology.

[111]  Yue-liang Chen,et al.  Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer. , 2005, World journal of gastroenterology.

[112]  M. Delano,et al.  Emerging implications of nanotechnology on cancer diagnostics and therapeutics , 2006, Cancer.

[113]  K. Jain,et al.  Nanotechnology-based Drug Delivery for Cancer , 2005, Technology in cancer research & treatment.

[114]  M. Busch,et al.  Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma , 2001, Transfusion.

[115]  Debashis Ghosh,et al.  alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. , 2002, JAMA.

[116]  P. Carpenter,et al.  A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. , 2001, Cancer research.

[117]  C C Schulman,et al.  PSA, PSA density, PSA density of transition zone, free/total PSA ratio, and PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0 ng/mL. , 1999, Urology.

[118]  Charles M. Lieber,et al.  Covalently functionalized nanotubes as nanometre- sized probes in chemistry and biology , 1998, Nature.

[119]  J. Joyce,et al.  Cysteine Cathepsins and the Cutting Edge of Cancer Invasion , 2007, Cell cycle.

[120]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[121]  M. Snyder,et al.  Protein chip technology. , 2003, Current opinion in chemical biology.

[122]  N. Morakkabati-Spitz,et al.  Paraneoplastic neurological syndrome: patient with anti-Yo antibody and breast cancer: a case report , 2003, Archives of Gynecology and Obstetrics.

[123]  K. Jain,et al.  Role of Nanobiotechnology in Developing Personalized Medicine for Cancer , 2005, Technology in cancer research & treatment.

[124]  D. Morton,et al.  Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients , 2004, Oncogene.

[125]  E. Petricoin,et al.  Early detection: Proteomic applications for the early detection of cancer , 2003, Nature Reviews Cancer.

[126]  S. Bates,et al.  Autoantibody cancer biomarker: extracellular protein kinase A. , 2006, Cancer research.

[127]  D. Turk,et al.  Lysosomal cysteine proteases (cathepsins): promising drug targets. , 2003, Acta crystallographica. Section D, Biological crystallography.

[128]  N. Rawlings,et al.  Evolutionary Lines of Cysteine Peptidases , 2001, Biological chemistry.

[129]  Vasilis Ntziachristos,et al.  Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[130]  W. Schlegel,et al.  Proteomics in cancer. , 2007, Advances in clinical chemistry.

[131]  T. Tani,et al.  Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma. , 2000, The American journal of pathology.

[132]  M. Abe,et al.  Magnetic carriers of iron nanoparticles coated with a functional polymer for high throughput bioscreening , 2006 .

[133]  J. Herman,et al.  Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. , 1999, Cancer research.

[134]  Y. Shoenfeld,et al.  Cancer and autoimmunity , 2002 .

[135]  E. Diamandis,et al.  Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications , 2002 .

[136]  A. Scorilas,et al.  mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy , 2006, Biological chemistry.

[137]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[138]  Christine A Iacobuzio-Donahue,et al.  Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. , 2003, Cancer research.

[139]  Bonnie F. Sloane,et al.  Cysteine cathepsins: multifunctional enzymes in cancer , 2006, Nature Reviews Cancer.

[140]  D. Katsaros,et al.  Higher human kallikrein gene 4 (KLK4) expression indicates poor prognosis of ovarian cancer patients. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[141]  D. Chan,et al.  Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer. , 2000, The Journal of urology.

[142]  R. Cote,et al.  Detection and clinical importance of micrometastatic disease. , 1999, Journal of the National Cancer Institute.

[143]  L. Huber Is proteomics heading in the wrong direction? , 2003, Nature Reviews Molecular Cell Biology.

[144]  R. Wolfert,et al.  A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. , 1997, Urology.

[145]  S. Ménard,et al.  High‐affinity monomeric 67‐kd laminin receptors and prognosis in pancreatic endocrine tumours , 1997, The Journal of pathology.

[146]  S. Bates,et al.  Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristate-lacking Calpha and RIIbeta subunit overexpression. , 2000, Proceedings of the National Academy of Sciences of the United States of America.