Analysis of the Expression of Peroxiredoxin I in Human Bladder Cancer

Eun Tak Kim; Hyuk Sagong; Wun-Jae Kim

doi:10.4111/kju.2008.49.4.300

Journal List > Korean J Urol > v.49(4) > 1005084

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kim, Sagong, and Kim: Analysis of the Expression of Peroxiredoxin I in Human Bladder Cancer

Original Article

Korean J Urol 2008;49(4):300-306.

Published online: 19 January 2008

DOI: https://doi.org/10.4111/kju.2008.49.4.300

Analysis of the Expression of Peroxiredoxin I in Human Bladder Cancer

Eun Tak Kim, Hyuk Sagong, Wun-Jae Kim¹

From the Department of Urology, College of Medicine, Eulji University, Daejeon, Chungbuk National University, Cheongju, Korea

¹Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea

Received 12 November 2007 Accepted 28 February 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Peroxiredoxins (PRDXs) are antioxidant enzymes that play an important role on cell differentiation, proliferation and apoptosis. In this study, we investigated if the expression levels of PRDX I were related to bladder cancer.

Materials and Methods

The mRNA level of PRDX I was examined via real time polymerase chain reaction (PCR) in 186 cancer specimens from patients with primary bladder cancer, 73 corresponding samples of normal looking bladder mucosae surrounding the cancer and 21 samples of normal bladder mucosae. We investigated the correlation between the expression levels of PRDX I and the clinico-pathological parameters of the 154 patients who could be followed up more than three years.

Results

The expression levels of PRDX I in bladder cancer (0.73pg/ml) were significantly higher that that in the normal bladder mucosae (0.04 pg/ml) (p＜0.01) or that in the corresponding normal bladder mucosae surrounding the cancer (0.38pg/ml) (p＜0.01). The expression level of PRDX I was not significantly enhanced in the non-recurred (0.87pg/ml) superficial bladder tumor patients compared with the recurred superficial bladder tumor patients (0.63pg/ml), but it was significantly enhanced in the non-progressed (0.82pg/ml) patients compared with the progressed (0.50pg/ml) patients (p＜0.05 for each).

Conclusions

An enhanced expression of PRDX I is strongly associated with the development of bladder cancer. Moreover, enhanced expressions of PRDX I are also positively associated with a low rate of progression of bladder cancer, and this might be useful as a marker for assessing progression in human bladder cancers.

Keywords: Peroxiredoxin I, Bladder tumor

REFERENCES

1.Popov Z., Hoznek A., Colombel M., Bastuji-Garin S., Lefrere-Belda MA., Bellot J, et al. The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder. Cancer. 1997. 80:1472–81.

2.Kausch I., Bohle A. Bladder cancer. II. Molecular aspects and diagnosis. Eur Urol. 2001. 39:498–506.

3.Kausch I., Bohle A. Molecular aspects of bladder cancer III. Prognostic markers of bladder cancer. Eur Urol. 2002. 41:15–29.

4.Finkel T., Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000. 408:239–47.

5.Kolonel LN., Hinds MW., Nomura AM., Hankin JH., Lee J. Relationship of dietary vitamin A and ascorbic acid intake to the risk for cancers of the lung, bladder, and prostate in Hawaii. Natl Cancer Inst Monogr. 1985. 69:137–42.

6.Ohnishi S., Murata M., Kawanishi S. Oxidative DNA damage induced by a metabolite of 2-naphthylamine, a smoking-related bladder carcinogen. Jpn J Cancer Res. 2002. 93:736–43.

7.Akcay T., Saygili I., Andican G., Yalcin V. Increased formation of 8-hydroxy-2′-deoxyguanosine in peripheral blood leukocytes in bladder cancer. Urol Int. 2003. 71:271–4.

8.Finkel T. Oxidant signals and oxidative stress. Curr Opin Cell Biol. 2003. 15:247–54.

9.Osada H., Takahashi T. Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene. 2002. 21:7421–34.

10.Halliwell B., Gutteridge JM., Cross CE. Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med. 1992. 119:598–620.

11.Chae HZ., Robison K., Poole LB., Church G., Storz G., Rhee SG. Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzy- mes. Proc Natl Acad Sci U S A. 1994. 91:7017–21.

12.Prosperi MT., Ferbus D., Karczinski I., Goubin G. A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. J Biol Chem. 1993. 268:11050–6.

13.Ishii T., Yamada M., Sato H., Matsue M., Taketani S., Nakayama K, et al. Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein. J Biol Chem. 1993. 268:18633–6.

14.Prosperi MT., Apiou F., Dutrillaux B., Goubin G. Organization and chromosomal assignment of two human PAG gene loci: PAGA encoding a functional gene and PAGB a processed pseudogene. Genomics. 1994. 19:236–41.

15.Lyu MS., Rhee SG., Chae HZ., Lee TH., Adamson MC., Kang SW, et al. Genetic mapping of six mouse peroxiredoxin genes and fourteen peroxiredoxin related sequences. Mamm Genome. 1999. 10:1017–9.

16.Prosperi MT., Ferbus D., Rouillard D., Goubin G. The pag gene product, a physiological inhibitor of c-abl tyrosine kinase, is overexpressed in cells entering S phase and by contact with agents inducing oxidative stress. FEBS Lett. 1998. 423:39–44.

17.Kinnula VL., Lehtonen S., Sormunen R., Kaarteenaho-Wiik R., Kang SW., Rhee SG, et al. Overexpression of peroxiredoxins I, II, III, V, and VI in malignant mesothelioma. J Pathol. 2002. 196:316–23.

18.Lehtonen ST., Svensk AM., Soini Y., Paakko P., Hirvikoski P., Kang SW, et al. Peroxiredoxins, a novel protein family in lung cancer. Int J Cancer. 2004. 111:514–21.

19.Noh DY., Ahn SJ., Lee RA., Kim SW., Park IA., Chae HZ. Overexpression of peroxiredoxin in human breast cancer. Anticancer Res. 2001. 21:2085–90.

20.Fujii J., Ikeda Y. Advances in our understanding of peroxi-redoxin, a multifunctional, mammalian redox protein. Redox Rep. 2002. 7:123–30.

21.Yanagawa T., Ishikawa T., Ishii T., Tabuchi K., Iwasa S., Bannai S, et al. Peroxiredoxin I expression in human thyroid tumors. Cancer Lett. 1999. 145:127–32.

22.Yanagawa T., Iwasa S., Ishii T., Tabuchi K., Yusa H., Onizawa K, et al. Peroxiredoxin I expression in oral cancer: a potential new tumor marker. Cancer Lett. 2000. 156:27–35.

23.Neumann CA., Krause DS., Carman CV., Das S., Dubey DP., Abraham JL, et al. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 2003. 424:561–5.

Table 1.

Clinico-pathological features of the 154 primary bladder transitional cell carcinomas

	Parameters		No. of patients
Sex	Male		126
Sex	Female		28
Age (years)	64.77±12.62
Stage	Superficial (107)	Ta	26
		T1	81
	Invasive (47)	T2	12
		T3	17
		T4	18
Grade		G1	31
		G2	71
		G3	52
Recurrence	Non-recurred		44
(in superficial tumors)	Recurred		63
Progression	Non-progressed		119
	Progressed		35
Cancer specific death			37

Table 2.

mRNA expression level (pg/ml) among the normal mucosae, the normal looking mucosae surrounding cancer and bladder cancer

	No. of patients	PRDX I
Bladder cancer	186	0.73±0.88*^,†
Normal	21	0.04±0.82
Surrounding normal^‡	73	0.38±0.64^§

^* : bladder cancer vs. normal mucosa: PRDX I, p＜0.01,

^† : bladder

^‡ : cancer vs. surrounding normal mucosa: PRDX I, p＜0.01,

^§ : normal bladder normal bladder mucosae surrounding cancer, mucosae surrounding cancer vs. normal mucosa: PRDX I, p＜0.01

Table 3.

The Peroxiredoxin I (PRDX I) expression levels with the stage and grade of bladder cancer

	No. of patients	PRDX I (pg/ml)	p-value
Stage
Superficial	107	0.77±0.88	0.66
Invasive	47	0.70±0.92	0.66
Grade
Low grade	102	0.65±0.79	0.07
High grade	52	0.95±1.03	0.07
Superficial bladder cancer
Low grade (Ta-1, G1-2)	92	0.68±0.82	0.04
High grade (T1, G3)	15	1.33±1.05	0.04
Invasive bladder cancer
Low grade	10	0.36±0.44	＜0.05
High grade	37	0.79±0.99	＜0.05

Table 4.

mRNA expression levels of peroxiredoxin I (PRDX I) in the superficial bladder cancer with recurrence

	No. of patients	PRDX I (pg/ml)	p-value
Non-recurrence	63	0.8703±0.9612	0.137
Recurrence	44	0.6264±0.7233	0.137
T1, G3 bladder cancer
Non-recurrence	9	1.6878±1.1303	0.079
Recurrence	6	0.7950±0.6839	0.079

Table 5.

mRNA expression levels of peroxiredoxin I (PRDX I) in the bladder cancer with progression

	No. of patients	PRDX I (pg/ml)	p-value
Non-progression	119	0.82±0.94	0.02
Progression	35	0.50±0.64	0.02
Superficial bladder cancer
Non-progression	94	0.83±0.90	＜0.01
Progression	13	0.32±0.43	＜0.01
T1, G3 bladder cancer
Non-progression	10	1.72±1.06	0.01
Progression	5	0.56±0.43	0.01
Invasive bladder cancer
Non-progression	25	0.78±1.07	0.53
Progression	22	0.61±0.73	0.53

TOOLS

Similar articles