UHRF1 is a Novel Diagnostic Marker of Lung Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2010 Jun 3

PMID 20517312

Citations 67

Authors

M Unoki

Y Daigo

J Koinuma

E Tsuchiya

R Hamamoto

Y Nakamura

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer is the leading cause of cancer deaths worldwide. As the sensitivity and specificity of current diagnostic markers are not perfect, we examined whether ubiquitin-like with PHD and ring finger domains 1 (UHRF1), which is overexpressed in various cancers but not yet examined in lung cancer in large scale, can be a novel diagnostic marker of lung cancer.

Methods: Immunohistochemical analysis using surgical specimens obtained from 56 US and 322 Japanese patients with lung cancer was performed.

Results: The UHRF1 was stained specifically in the nuclei of cancer cells, but not in the other cells. The UHRF1 expression was observed in all histological types of lung cancer, especially in non-adenocarcinomas (non-ADCs), both in the US and Japanese cases. In 322 Japanese non-small cell lung cancer (NSCLC) cases, UHRF1 expression was associated with the histological type (higher in non-ADCs; P<0.00001), gender (higher in male; P=0.00082), smoking (higher in smokers; P=0.00004), pT factor (higher in advanced stage; P=0.00010), and pN factor (higher in cancers with metastasis in regional lymph nodes; P=0.00018). The UHRF1 expression was also associated with poor prognosis for NSCLC patients (P=0.0364). Although UHRF1 overexpression was associated with these malignant indicators, UHRF1 was detectable in half of lung cancer patients in an early pathological stage.

Conclusion: The UHRF1 is overexpressed in various types of lung cancer from early pathological stage. Therefore, detection of UHRF1 expression in tissue specimens by immunohistochemistry can be useful for diagnosis of lung cancer in all pathological stages.

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References

Karagianni P, Amazit L, Qin J, Wong J . ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation. Mol Cell Biol. 2007; 28(2):705-17. PMC: 2223417. DOI: 10.1128/MCB.01598-07. View

Lorenzato M, Caudroy S, Bronner C, Evrard G, Simon M, Durlach A . Cell cycle and/or proliferation markers: what is the best method to discriminate cervical high-grade lesions?. Hum Pathol. 2005; 36(10):1101-7. DOI: 10.1016/j.humpath.2005.07.016. View

Crnogorac-Jurcevic T, Gangeswaran R, Bhakta V, Capurso G, Lattimore S, Akada M . Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterology. 2005; 129(5):1454-63. DOI: 10.1053/j.gastro.2005.08.012. View

Daigo Y, Nakamura Y . From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg. 2008; 56(2):43-53. DOI: 10.1007/s11748-007-0211-x. View

Taniwaki M, Daigo Y, Ishikawa N, Takano A, Tsunoda T, Yasui W . Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer. Int J Oncol. 2006; 29(3):567-75. View

Asamura H, Goya T, Koshiishi Y, Sohara Y, Eguchi K, Mori M . A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers. J Thorac Oncol. 2008; 3(1):46-52. DOI: 10.1097/JTO.0b013e31815e8577. View

Achour M, Fuhrmann G, Alhosin M, Ronde P, Chataigneau T, Mousli M . UHRF1 recruits the histone acetyltransferase Tip60 and controls its expression and activity. Biochem Biophys Res Commun. 2009; 390(3):523-8. DOI: 10.1016/j.bbrc.2009.09.131. View

Ando S, Kimura H, Iwai N, Kakizawa K, Shima M, Ando M . The significance of tumour markers as an indication for mediastinoscopy in non-small cell lung cancer. Respirology. 2003; 8(2):163-7. DOI: 10.1046/j.1440-1843.2003.00443.x. View

Jenkins Y, Markovtsov V, Lang W, Sharma P, Pearsall D, Warner J . Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth. Mol Biol Cell. 2005; 16(12):5621-9. PMC: 1289407. DOI: 10.1091/mbc.e05-03-0194. View

10.

Furukawa C, Daigo Y, Ishikawa N, Kato T, Ito T, Tsuchiya E . Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res. 2005; 65(16):7102-10. DOI: 10.1158/0008-5472.CAN-04-1877. View

11.

Hopfner R, Mousli M, Jeltsch J, Voulgaris A, Lutz Y, Marin C . ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression. Cancer Res. 2000; 60(1):121-8. View

12.

Avvakumov G, Walker J, Xue S, Li Y, Duan S, Bronner C . Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 2008; 455(7214):822-5. DOI: 10.1038/nature07273. View

13.

Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M . Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008; 455(7214):818-21. DOI: 10.1038/nature07249. View

14.

Unoki M, Nishidate T, Nakamura Y . ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004; 23(46):7601-10. DOI: 10.1038/sj.onc.1208053. View

15.

Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo T . The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007; 450(7171):908-12. DOI: 10.1038/nature06397. View

16.

Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T . A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 2005; 65(13):5638-46. DOI: 10.1158/0008-5472.CAN-05-0600. View

17.

Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H . Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007; 67(24):11601-11. DOI: 10.1158/0008-5472.CAN-07-3243. View

18.

Toyoda Y, Nakayama T, Ioka A, Tsukuma H . Trends in lung cancer incidence by histological type in Osaka, Japan. Jpn J Clin Oncol. 2008; 38(8):534-9. PMC: 2525496. DOI: 10.1093/jjco/hyn072. View

19.

Wakai K, Inoue M, Mizoue T, Tanaka K, Tsuji I, Nagata C . Tobacco smoking and lung cancer risk: an evaluation based on a systematic review of epidemiological evidence among the Japanese population. Jpn J Clin Oncol. 2006; 36(5):309-24. DOI: 10.1093/jjco/hyl025. View

20.

Jin W, Chen L, Chen Y, Xu S, Di G, Yin W . UHRF1 is associated with epigenetic silencing of BRCA1 in sporadic breast cancer. Breast Cancer Res Treat. 2009; 123(2):359-73. DOI: 10.1007/s10549-009-0652-2. View