Cell-Free DNA Source of Cell-Free DNA DNA in Urine Other Cancer Indicators Indicator Limitations

Other Cancer Indicators

Apart from increased DNA levels, increased levels of albumin in circulation may also be used as an indicator of disease state. Pugia et al. (1999) report that majority of patients suffered albuminuria, while healthy individuals did not have increased values. The highest prevalence of positive protein excretion occurred in patients with kidney disease of any type; patients with cancer also exhibited albuminuria.

Rozalski et al. (2002) examined urine samples from patients with breast, lung, or prostate cancers (all with metastasis of their primary tumours into the bones) for the altered DNA base 8-hydroxyguanine. 8-hydroxyguanine is thought to be a repair product of oxidative DNA damage, and has been correlated with carcinogenesis in vivo (Rozalski et al. 2002). This study found that the concentration of 8-hydroxyguanine in urine from cancer patients, regardless of primary cancer type, was significantly higher than that in healthy controls (Rozalski et al. 2002). Thus, new markers found in urine may complement the measurement of total concentration of urinary DNA in diagnostic or prognostic applications. Below is a table of other markers found in the urine that have been positively correlated to cancer.

Authors (year)	Type of Cancer	Cancer Marker	Results
Groskopf et al., (2006)	Prostate	PCA3 gene mRNA which can be detected with a prostate specific antigen (PSA)	There was a reported 79% sensitivity to this specific mRNA
Theodorescu et al., (2005)	Prostate	Specific polypeptides	Capillary electrophoresis with MS to identify prostate cancer with 92% sensitivity and 96% specificity
Hutchinson et al., (2005)	Prostate	Thymosin beta 15	Biomarker found in tissue sample combined with PSA is a reported as a viable diagnostic tool for detection of prostate cancer
Chan et al., (2004)	Cancer survival	Matrix metaloproteinases (MMP) and vascular endothelial growth factor (VEGF)	Measured in urine and exhibit trends that could be predictive markers for 1 year survival
Di Carlo et al., (2006)	Bladder cancer	MMP9; tissue polypeptide-specific antigen (TPS) and protein 22 of nuclear matrix (NMP-22)	All markers were found to be highest in advanced stages bladder cancer and MMP9 in elevated levels of urine of those with bladder cancer
Grossman et al, (2006)	Bladder cancer	NMP-22	Able to confirm 102 of 103 bladder cancer cases compared to 94 of 103 samples detected by traditional cystoscopy
Xianghua et al, (2002)	Renal cell carcinoma	VEGF, MMP2, MMP9	Elevated levels of VEGF in those with renal cell carcinoma, and MMP2 and MMP9 can be correlated to tumor stage grade and survival probability
Irmak et al., (2005)	Bladder	Orosomucoid (ORM) and human zinc-alpha(2)-glycoprotein (ZAG)	Two specific proteins found in increased concentration in samples with cancer as compared to controls. Levels highest as the cancer was more invasive.
Mueller et al., (2005)	---	Protein expression profiles	Specific protein signatures in urine could be of value for diagnosis.
Iwaki et al., (2004)	Bladder	Calreticulin (CRT), gamma-synuclein (SNCG) and catechol-o-methyltransferase (s-COMT	Potential urinary markers of bladder cancer, sensitivity of 76.8% and specificity of 77.4%
Tantipaiboonwong et al., (2005)	Lung	CD59 glycoprotein, transthyretin (TTR), GM2 activator protein (GM2AP) and Ig-free ligh chain	Protein expression of the mentioned proteins were different when compared to normal patients
Lynch et al., (2001)	Myeloma	Monoclonal immunoproteins	May be linked to some forms of cancer but not yet conclusive
Roy et al., (2004)	Breast	ADAM 12	Patients with breast cancer had significantly higher amounts of ADAM 12 in urine than in controls
Hou et al., (2003)	Breast	Deoxypyridinoline	Study showed that the ratio of deoxypyridinoline/ creatinine in women with breast cancer was much higher in women with bone metastasis with metastatic breast cancer
Kuranishi (1996)	Tumors related to lung, hepatocellular carcinoma, gastric cancer	Transforming growth factor beta (TGF-beta)	Found in urine it is a positive marker for pneumonia, liver cirrhosis and mentioned forms of cancer. In malignant group, sensitivity was 75% and specificity was 72.7 %.

Table 3. Summary of the current literature on other potential markers found in urine that may be correlated to cancer.

Chan L.W, Moses M.A, Goley E, Sproull M, Muanza T, Coleman C.N, Figg W.D, Albert P.S, Ménard C, Camphausen K. Urinary VEGF and MMP levels as predictive markers of 1-year progression-free survival in cancer patients treated with radiation therapy: A longitudinal study of protein kinetics throughout tumor progression and therapy. J Clin Onc 2004; 22(3): 499-506.

Di Carlo A, Terracciano D, Mariano A, Macchia V. Urinary gelatinase activities (matrix metalloproteinases 2 and 9) in human bladder tumors. Oncology Rep 2006; 15(5): 1321-1326.

Groskopf J, Aubin SMJ, Deras IL, Blase A, Bodrug S, Clark C, Brentano S, Mathis J, Pham J, Meyer T, Cass M, Hodge P, Macairan ML, Marks LS, Rittenhouse H. APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer. Clin Chem 2006; 52: 1089-1095.

Grossman BH, Soloway M, Messing E, Katz G, Stein B, Kassabian V, Shen Y. Surveillance for recurrent bladder cancer using a point-of-care proteomic assay. J Amer Med Assoc 2006; 295(3): 299-305.

Hou MF, Lin SB, Yuan SSF, Tsai LY, Tsai SM, Hsieh JS, Huang TJ. Diagnostic value of urine deoxypyridinoline for detecting bone metastases in breast cancer patients. Annals Clin Lab Science 2003; 33(1): 55-61.

Hsiao JR, Jin YT, Tsai ST. Detection of cell free Epstein-Barr virus DNA in sera from patients with nasopharyngeal carcinoma. Cancer 2002; 94: 723-729.

Hutchinson L, Chang EL, Becker CM, Shih MC, Brice M, DeWolf WC, Gaston SM, Zetter BR. Use of thymosin beta 15 as a urinary biomarker in human prostate cancer. Prostate 2005; 64(2): 116-127.

Irmak S, Tilki D, Heukeshoven J, Oliveira FL, Friedrich M, Huland H, Erguen S. Stage-dependent increase of orosomucoid and zinc-alpha(2)-glycoprotein in urinary bladder cancer. Proteomics 2005; 5(16): 4296-4304.

Iwaki H, Kageyama S, Isono T, Wakabayashi Y, Okada Y, Yoshimura K, Terai A, Arai Y, Iwamura H, Kawakita M, Yoshiki T. Diagnostic potential in bladder cancer of a panel of tumor markers (calreticulin, gamma-synuclein, and catechol-o-methyltransferase) identified by proteomic analysis. Cancer Science 2004; 95(12): 955-961.

Kuranishi F.Detection of urinary TGF-beta as a tumor marker. Med J Hiroshima Univer 1996; 44(6): 319-341.

Lynch HT, Sanger WG, Pirruccello S, Quinn-Laquer B,Weisenburger DD. Familial multiple myeloma: A family study and review of the literature. J Nat Cancer Institute 2001; 93: 1479-1483.

Mueller J, von Eggeling F, Driesch D, Schubert J, Melle C, Junker K. ProteinChip technology reveals distinctive protein expression profiles in the urine of bladder cancer patients. Euro Urology 2005; 47(6): 885-894.

Nawroz H, Koch W, Anker P, Stroun M, Sidransky D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat Med 1996; 2:1035-1037.

Pugia MJ, Lott JA, Profitt JA, Cast TK. High-sensitivity dye binding assay for albumin in urine.J Clin Lab Anal. 1999;13(4):180-7.

Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J Bio Chem 2004; 279(49): 51323-51330.

Rozalski R, Gackowski D, Roszkowski K, Foksinski M, Olinski R. The level of 8-hydroxyguanine, a possible repair product of oxidative DNA damage, is higher in urine of cancer patients than in control subjects. Cancer Epidemiol Biomarkers Prev 2002; 11: 1072-1075.

Tantipaiboonwong P, Sinchaikul S, Sriyam S, Phutrakul S, Chen ST. Different techniques for urinary protein analysis of normal and lung cancer patients. Proteomics 2005; 5(4): 1140-1149.

Theodorescu D, Fliser D, Wittke S, Mischak H, Krebs R, Walden M, Ross M, Eltze E, Bettendorf O, Wulfing C, Semjonow A. Pilot study of capillary electrophoresis coupled to mass spectrometry as a tool to define potential prostate cancer biomarkers in urine. Electrophor 2005; 26(14): 2797-2808.

Xianghua Z, Motoki Y, Hirotsugu U, Yoshiyuki K. Angiogenesis in renal cell carcinoma: Evaluation of microvessel density, vascular endothelial growth factor and matrix metalloproteinases. Internat J Urology 2002: 9(9): 509.

Start of Page

Donations:

Donations are welcome (and appreciated) to help our cancer testing research, all contributors are welcome to submit multiple pictures of their group or fund raising activity to our Donation Album. To donate go to our Donation Page.

See our brochure:

(in .pdf format):