The proliferation marker thymidine kinase 1 in clinical use (Review)

Zhou,Ji; He,Ellen; Skog,Sven

doi:10.3892/mco.2012.19

The proliferation marker thymidine kinase 1 in clinical use (Review)

Authors:
- Ji Zhou
- Ellen He
- Sven Skog
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Affiliations: Sino-Swed Molecular Bio-Medicine Research Institute, Shenzhen 518057, P.R. China
Published online on: September 4, 2012 https://doi.org/10.3892/mco.2012.19
Pages: 18-28

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Abstract

Tumor-related biomarkers are used for the diagnosis, prognosis and monitoring of treatments and follow-up of cancer patients, although only a few are fully accepted for the detection of invisible/visible tumors in health screening. Thymidine kinase 1 (TK1), a cell cycle‑dependent and thus a proliferation‑related marker, has been extensively studied during the last decades, using both biochemical and immunological techniques. Therefore, TK1 is an emerging potential proliferating biomarker in oncology that may be used for the prognosis and monitoring of tumor therapy, relapse and survival. In addition, TK1 concentration in serum (STK1p) is a useful biomarker in healthy screening for the detection of potential malignancy development as well as the identification of early‑stage tumors, with a few false-positive cases (ROC value, 0.96; tumor proliferation sensitivity, 0.80; specificity, 0.99). In this review, we examine results regarding the expression of STK1p and TK1 in relation to cancer patients and STK1p in health screening published between 2000 and 2012. The use of tumor-related markers recommended by international cancer organizations is also discussed. This review provides valuable information for applications in tumor patients, in health screening and for cancer research.

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1.	Gronowitz JS, Hagberg H, Kallander CF and Simonsson B: The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin’s lymphoma. Br J Cancer. 47:487–495. 1983.
2.	Wu CJ, Yang RJ, Zhou J, Bao S, Zou L, Mao YR and He Q: Production and characterisation of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1. J Immunol Methods. 277:157–169. 2003.
3.	O’Neill KL, Buckwalter MR and Murray BK: Thymidine kinase: diagnostic and prognostic potential. Expert Rev Mol Diagn. 1:428–433. 2001.
4.	Topolcan O and Holubec L Jr: The role of thymidine kinase in cancer diseases. Expert Opin Med Diagn. 2:129–141. 2008.
5.	von Euler H and Eriksson S: Comparative aspects of the proliferation marker thymidine kinase 1 in human and canine tumour diseases. Vet Comp Oncol. 9:1–15. 2011.
6.	He E, Xu XH, Guan H, Chen Y, Chen ZH, Pan ZL, Tang LL, Hu GZ, Li Y, Zhang M, et al: Thymidine kinase 1 is a potential marker for prognosis and monitoring the response to treatment of patients with breast, lung, and esophageal cancer and non-Hodgkin’s lymphoma. Nucleosides Nucleotides Nucleic Acids. 29:352–358. 2010.
7.	Aufderklamm S, Todenhöfer T, Gakis G, Kruck S, Hennenlotter J, Stenzl A and Schwentner C: Thymidine kinase and cancer monitoring. Cancer Lett. 316:6–10. 2012.
8.	Wu James T: Circulating Tumor Markers of the New Millennium. AACC Press; New York: pp. 115–117. 2002
9.	Al-Madhoun A, Tjarks W and Eriksson S: The role of thymidine kinases in the activation of pyrimidine nucleoside analogues. Mini Rev Med Chem. 4:341–350. 2004.
10.	Jirawatnotai S, Hu Y, Michowski W, Elias JE, Becks L, Bienvenu F, Zagozdzon A, Goswami T, Wang YE, Clark AB, et al: A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. 474:230–234. 2011.
11.	Cigna: Markers for diagnosis and management of cancer. USA, http://www.cigna.com. Accessed November 15, 2011.
12.	Munch-Petersen B: Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. Nucleosides Nucleotides Nucleic Acids. 29:363–369. 2010.
13.	Chen YL, Eriksson S and Chang ZF: Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage. J Biol Chem. 285:27327–27335. 2010.
14.	Gasparri F, Wang N, Skog S, Galvani A and Eriksson S: Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan assays. Eur J Cell Biol. 88:779–785. 2009.
15.	He Q, Zou L, Zhang PA, Lui JX, Skog S and Fornander T: The clinical significance of thymidine kinase 1 measurements in serum of breast cancer patients using anti-TK1 antibody. Int J Biol Markers. 15:139–146. 2000.
16.	Zou L, Zhang PG, Zou S, Li Y and He Q: The half-life of cytosolic thymidine kinase in serum by ECL dot bolt potential marker for monitoring the response to surgery of patients with gastric cancer. Int J Biolog Markers. 17:135–140. 2002.
17.	Li HX, Zhang S, Lei DS, Wang XQ, Skog S and He Q: Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer. Oncol Rep. 13:145–149. 2005.
18.	He Q, Zhang P, Zou L, Li H, Wang X, Zhou S, Fornander T and Skog S: Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. Oncol Rep. 14:1013–1019. 2005.
19.	Zhang J, Jia Q, Zou S, Zhang P, Zhang X, Skog S, Luo P, Zhang W and He Q: Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients. Oncol Rep. 15:455–461. 2006.
20.	He Q, Fornander T, Johansson H, Johansson U, Hu GZ, Rutqvist LE and Skog S: Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer. Anticancer Res. 26:4753–4759. 2006.
21.	Xu XH, Zhang YM, Shu XH, Shan LH, Wang ZW, Zhou YL, Wen HK, He F, He E and Skog S: Serological thymidine kinase 1 reflects progression of pre-malignant and malignant tumours during therapy. Mol Med Rep. 1:705–712. 2008.
22.	Zhang GQ, Jiao SC and Wei XF: Serum thymidine kinase 1: a proliferation marker for neoplasms in oncologic monitoring of elderly people. J Modern Oncol. 16:831–832. 2008.(In Chinese).
23.	Chen ZH, Zhou H, Tian NB, et al: Serological thymidine kinase 1 (STK1) indicates an elevated risk for development of malignant tumours. Anticancer Res. 28:3897–3907. 2008.
24.	Zhang XH, Yang JR, Fu XY, Liu HX, Yun X, Song B, Zhang M, He E and Skog S: The significance of serum thymidine kinase 1 for the risk screening of cancer development in pre-cancerous diseases. Chin J Health Manag. 4:35–38. 2010.
25.	Huang SQ, Lin J, Guo N, Zhang M, Yun X, Liu S, Zhou J, He E and Skog S: Elevated serum thymidine kinase 1 predicts risk of pre/early cancerous progression. Asian Pac J Cancer Prev. 12:497–505. 2011.
26.	Chen ZH, Huang SQ, Wang Y, Yang AZ, Wen J, Xu XH, Chen Y, Chen QB, Wang YH, He E, Zhou J and Skog S: Serological thymidine kinase 1 is a biomarker for early detection of tumours - a health screening study on 35,365 people, using a sensitive chemiluminescent dot blot assay. Sensors (Basel). 11:11064–11080. 2011.
27.	Chen ZH, Wang YQ, Zhu XL, Zhou H, Liu Y, Yang PT and Cao X: Thymidine kinase 1 measurement in health check up. Chin J Health Manag. 45:349–351. 2011.
28.	Yuan ZY, Liu XA, Ling LJ, Zhao Y and Wang S: The significance of serum thymidine kinase 1 on assistant diagnosis and evaluation of chemotherapy effect on breast cancer patients operated. Acta Univ Med Nanjiang (Natural Science). 30:1002–1004. 2010.
29.	Huang H and Luo YL: The role of serum thymidine kinase 1 levels in the postoperative evaluation of curative effect of breast cancer. Lab Med. 26:79–81. 2011.(In Chinese).
30.	Chen QB, Li CC, Zhao R, Dia Y, Chen QJ and Chen WY: The application study on serum thymidine kinase 1 level changes for diagnosis and therapy of breast cancers. Appl Med. 28:39–41. 2012.
31.	Carlsson L, Larsson A and Lindman H: Elevated levels of thymidine kinase 1 peptide in serum from patients with breast cancer. Ups J Med Sci. 114:116–120. 2009.
32.	Chen FY, Tang LL and Huang X: STK1 assay in patients with breast cancer before and after neo-adjuvant chemotherapy. Chin Tumor Clin. 6:732–735. 2009.
33.	Lu J, Chen KM, Wang ZM, Wu CY and Zhou QH: Correlativity study on CT and serum thymidine kinase 1 of breast diseases. Chin J CT MNR. 7:22–24. 2009.
34.	Zhang ZY, Chen M, Fan L and Dong RF: Serum TK1 concentration and clinical significance in patients with cervical carcinoma. Jilin Med. 32:7438–7439. 2012.
35.	Cheng XW, Yang YX, Yu XY and Liu YP: Expression of SCC-Ag and TK1 in middle-advanced cervical carcinoma and the significance in treatment. Chin J New Drugs. 20:1208–1300. 2011.
36.	Chen Y, Ying M, Chen Y, Hu M, Lin Y, Chen D, Li X, Zhang M, Yun X, Zhou J, He E and Skog S: Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings. Int J Clin Oncol. 15:359–368. 2010.
37.	Li Z, Wang Y, He J, Ma J, Zhao L, Chen H, Li N, Zhou J, He E and Skog S: Serological thymidine kinase 1 is a prognostic factor in esophagus, cardiac and lung carcinomas. Eur J Cancer Prev. 9:313–318. 2010.
38.	Guo L and Lu RQ: Significance of serum thymidine kinase determination in patients with gastric carcinoma. Lab Med. 23:271–273. 2008.
39.	Xu LB, Shen LQ and Zhuang ZX: The expression and clinical significance of serumTK-1 in gastrointestinal tumors. J Clin Med Prac. 17:20–23. 2011.(In Chinese).
40.	Shen Z, Chen Z, Xu R, Zhang J and Jiang H: Evaluation of the significance of serum thymidine kinase 1 detection in the diagnosis and curative effect of gastrointestinal malignant tumors. Exp Lab Med. 5:531–533. 2011.(In Chinese).
41.	Jiao JH, Huan X and Shi RH: Research of thymidine kinase1 (TK1) in diagnosis and follow-up of colorectal carcinoma. J Clin Med Prac. 15:21–23. 2011.
42.	Xing H and Zhang ZF: Expression and clinical significance of serum TK1, OPN and CEA in patients with colorectal carcinoma. J Community Med. 9:15–18. 2011.
43.	Tian JG, Jia YD and Liu HT: Serum TK1, EGF, HGF and CRP and IL-6 levels in patients with colon cancer using laparoscopic and open surgery. Shangdong Med. 50:42–43. 2011.
44.	Zhang YC: Clinical significance of serum thymidine kinase 1 with colorectal carcinomas. J Med Forum. 130:28–30. 2009.
45.	Wei JW, Xu CR, Zen DZ and Chen Y: Analysis on the content of TK1 of patients with colonic polyps. Lab Med Clin. 8:769–701. 2011.
46.	Li SJ, Wu G, Ye J, Zhang X, Cheng F and Zhang KQ: The meaning of blood serum thymidine kinase level in early screening for prostatic carcinoma. Immun J. 27:459–461. 2011.
47.	Luo P, He E, Eriksson S, Zhou J, Hu G, Zhang J and Skog S: Thymidine kinase activity in serum of renal cell carcinoma patients is a useful prognostic marker. Eur J Cancer Prev. 18:220–224. 2009.
48.	Yuan H, Zhu B, Wu YW and Zhou JT: Clinical significance of determination of changes of serum TK1 level in patients with lung cancer. J Radioimmunol. 24:301–302. 2011.(In Chinese).
49.	Zhou Y, Wang D, Yang AZ, He E, Skog S and Zhang M: Clinical significant of detecting serum thymidine kinase1 in diagnostic and prognosis evaluation of lung cancers. Jiangshu Med. 38:310–313. 2012.
50.	Guan Y, Guo QS, Shan FL and Liu IJ: Expression and significance of thymidine kinase 1 in small cell lung carcinoma tissues. Chin J Cancer Prev Treat. 17:746–748. 2010.
51.	Feng MH: The significance of the detection of serum thymidine kinase in treatment assessment of lung carcinomas. J Radioimmunol. 24:455–456. 2011.
52.	Xu W, Shen QD and Yu H: Serum thymidine kinase and LPL and its associated prognostic factors in chronic lymphocytic leukemia. Chin J Hematol. 30:23–26. 2009.
53.	Xu W, Cao X, Miao KR, Qiao C, Wu YJ, Liu Q, Fan L and Li JY: Serum thymidine kinase 1 concentration in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors. Int J Hematol. 90:205–211. 2009.
54.	Zeng ZJ, Uyang WT, Sun YH and Cai XH: Clinical significance of thymidine kinase 1 in chemotherapy of leukemia. J Mol Diagn Ther. 1:28–31. 2009.
55.	Pan ZL, Ji XY, Shi YM, Zhou J, He E and Skog S: Serum thymidine kinase 1 concentration as a prognostic factor of chemotherapy-treated non-Hodgkin’s lymphoma patients. J Cancer Res Clin Oncol. 136:1193–1199. 2010.
56.	Chen QB, Liu RP, Huang H, Li Q, Zhang JY, Zhen SB, Li Q, Jing N and Zhen L: Serum thymidine kinase 1 and its role in monitoring and prognosis of tumor. Guangdong Med. 29:1022–1024. 2008.
57.	Li QR, Yuan H, Sang SB, Su CH, Wu YW, Zhang M, Zhou J, Zhao JT, He E and Skog S: The significance of serum thymidine kinase 1 for early tumor detection and monitoring the response to therapy. Chin J Nuclear Med. 29:271–273. 2009.
58.	Wang LJ: Clinical significance of cytoplasmic thymidine kinase in patients with malignant tumors. Heilongjiang Med. 24:904–905. 2011.
59.	Wang ZX, Zhang B, Ni B and Zhan J: Value of serum thymidine kinase 1 in evaluating the efficacy of malignant tumor treatment. Jiangsu Med J. 18:2174–2175. 2011.(In Chinese).
60.	Mao RY, Wu JP, Wang N, He LX, Wu CJ, He Q and Skog S: A comparison study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer. Cancer Invest. 20:922–931. 2002.
61.	Wu JP, Mao YR, He LX, Wang N, Wu CJ, He Q and Skog S: Comparison study on the expression of cytosolic thymidine kinase and proliferating cell nuclear antigen in colorectal carcinoma. Anticancer Res. 20:4815–4820. 2000.
62.	He Q, Mao Y, Wu J, Decker C, Merza M, Wang N, Eriksson S, Castro J and Skog S: Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas. Int J Oncol. 25:945–953. 2004.
63.	Mao YR, Wu JP, Skog S, Eriksson S, Zhao Y, Zhou J and He Q: Expression of cell proliferating genes in patients with non-small-cell lung cancer (NSCLC) by immunohistochemistry and cDNA profiling. Oncol Rep. 13:837–846. 2005.
64.	Guan H, He E, Zhou J, Li Y, Eriksson S and Skog S: Thymidine kinase 1 expression is significantly different in breast benign (UDH), and in pre-malignant (ADH), primary tumour in situ (DCIS) and invasive ductal (IDC) of breast carcinoma. Mol Med Rep. 2:923–929. 2009.
65.	Liu C, Gao Q, Shi QL, Yu B, Ma HH, Eriksson S, He E and Skog S: Significance of TK1 and Ki-67 expression in ovarian serous adenocarcinoma. J Clin Exp Pathol. 27:1289–1293. 2011.
66.	Xu Y, Shi QL, Ma H, Zhou H, Lu Z, Yu B, Zhou X, Eriksson S, He E and Skog S: High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma. Tumour Biol. 33:475–483. 2012.
67.	Luo P, Wang N, He E, Eriksson S, Zhou J, Hu G, Zhang J and Skog S: The proliferation marker thymidine kinase 1 level is high in normal kidney tubule cells compared to other normal and malignant renal cells. Pathol Oncol Res. 16:277–283. 2010.
68.	Gakis G, Hennenlotter J, Scharpf M, Hevler J, Schilling D, Kuehs U, Stenzl A and Schwentner C: XPA-210: a new proliferation marker to characterize tumor biology and progression of renal cell carcinoma. World J Urol. 29:801–806. 2011.
69.	Ye FP, Xie QL, Liu XL, Zhen JH, Lan JL and Yu M: Expression of TK1 and Ki67 in prostate diseases. J Clin Exp Pathol. 24:644–667. 2008.
70.	Aufderklamm S, Hennenlotter J, Todenhoefer T, Gakis G, Schilling D, Vogel U, Kuehs U, Dlugosch J, Knapp J, Merseburger A, et al: XPA-210: a new proliferation marker determines locally advanced prostate cancer and is a predictor of biochemical recurrence. World J Urol. Oct 4–2011, (Epub ahead of print).
71.	Yang L, Parkin DM, Ferlay J, Li L and Chen Y: Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev. 14:243–250. 2005.
72.	Barregard L, Holmberg E and Sallsten G: Leukaemia incidence in individualsliving close to an oil refinery. Environ Res. 109:985–990. 2009.
73.	Berman JJ and Moor GW: Precancer: The Beginning and the End of Cancer. Jones and Bartlett Learning Inc.; Boston: 2010
74.	Nisman B, Allweis T, Kaduri L, Maly B, Gronowitz S, Hamburger T and Peretz T: Serum thymidine kinase 1 activity in breast cancer. Cancer Biomark. 7:65–72. 2010.
75.	Kemik O, Kemik AS, Purisa S and Tuzun S: Serum thymidine kinase is associated with gastric adenocarcinoma. Bratisl Lek Listy. 112:510–511. 2011.
76.	Letocha H, Eklov S, Gronowitz S, Johan BN and Nilsson S: Deoxythymidine kinase in the staging of prostatic adenocarcinoma. Prostate. 29:15–19. 1996.
77.	Nisman B, Yutkin V, Nechushtan H, Gofrit ON, Peretz T, Gronowitz S and Pode D: Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy. Urology. 76:513–516. 2010.
78.	Konoplev SN, Fritsche HA, O’Brien S, Wierda WG, Keating MJ, Gornet TG, St Romain S, Wang X, Inamdar K, Johnson MR, et al: High serum thymidine kinase 1 level predicts poorer survival in patients with chronic lymphocytic leukemia. Am J Clin Pathol. 134:472–477. 2010.
79.	Procházka V, Faber E, Raida L, Langová K, Indrák K and Papajík T: High baseline serumthymidine kinase 1 level predicts unfavorable outcome in patients with follicular lymphoma. Leuk Lymphoma. 53:1306–1310. 2012.