Lung cancer is the leading cause of cancer deaths worldwide including the United States and Japan according to the World Health Organization (WHO) database (http://www.who.int/en/
). Among various histological types of lung cancers, non-small cell lung cancer (NSCLC) accounts for approximately 80%, whereas small cell lung cancer (SCLC) accounts for approximately 15%. The two major histological types of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma (SCC). In Japan, SCC accounts for 34.7% and 16.3% of all lung cancer cases in males and females, respectively. On the other hand, ADC accounts for 42.9% and 67.2% of all lung cancer cases in males and females, respectively (incident year 1999–2003; Toyoda et al, 2008
). The remaining few per cent of NSCLC are other histological types of carcinomas including large cell carcinoma and adenosquamous cell carcinoma; SCC is more common in males, and smoking dramatically increases the risk of this type of cancer; the relative risks of smoking in males were 11.7 and 2.3 for SCC and ADC, respectively, and were 11.3 and 1.4 correspondingly in females in Japan (Wakai et al, 2006
). Smoking rates of Japanese males and females in 2007 are 43.3% and 12.0%, respectively, according to Japanese exposure factors handbook published by National Institute of Advanced Industrial Science and Technology in Japan (http://unit.aist.go.jp/riss/crm/exposurefactors/english_summary.html
). The 5-year survival rate based on pathologic (p) stages was analysed using a large population of Japanese lung cancer cases (n
010) in 2005 (Asamura et al, 2008
). According to the study, the 5-year survival rates of SCLC patients who underwent plumonary resections were as follows: 58.3%, 60.2%, 40.6%, 41.1%, 28.3%, 34.6%, and 30.8% for IA, IB, IIA, IIB, IIIA, IIIB, and IV, respectively. The 5-year survival rates of NSCLC patients who underwent plumonary resections were as follows: 83.9%, 66.3%, 61.0%, 47.4%, 32.8%, 29.6%, and 23.1% for IA, IB, IIA, IIB, IIIA, IIIB, and IV, respectively. This study also showed that ADC histological type, female gender, and age <50 years were significant favourable prognostic factors.
Although there are several biomarkers in clinical use such as SCC antigen, carcinoembryonic antigen, neuron-specific enolase, and pro-gastrin-releasing peptide, none of them are perfect in terms of sensitivity and/or specificity (Ando et al, 2003
; Molina et al, 2005
). Thus, we have been seeking additional sensitive and cancer-specific biomarkers detectable in serum and tumour tissues to improve the current high mortality of lung cancer, and found more than 20 candidate diagnostic and/or prognostic biomarkers, which are now under development for clinical use (Daigo and Nakamura, 2008
). As many molecular signalling pathways are disrupted during lung carcinogenesis, we believe that combinations of biomarkers are necessary for precise diagnosis and prognosis of lung cancer, and thus we continue to search for superior biomarkers.
Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), also known as ICBP90, was identified as a protein whose expression is only detectable in proliferating cells, not in quiescent cells (Hopfner et al, 2000
; Unoki et al, 2004
). Recently, it was revealed that UHRF1 has a central function in epigenetic modulation during DNA duplication in the S phase (Sharif et al, 2007
; Arita et al, 2008
; Avvakumov et al, 2008
; Hashimoto et al, 2008
). Up-regulation of UHRF1 has been reported in various cancers (Mousli et al, 2003
; Crnogorac-Jurcevic et al, 2005
; Jenkins et al, 2005
; Lorenzato et al, 2005
; Oba-Shinjo et al, 2005
; Pita et al, 2009
; Unoki et al, 2009
). As no large-scale study of UHRF1 expression in lung cancers has been performed, we examined whether UHRF1 could be a novel diagnostic marker of lung cancer by immunohistochemical analysis to understand the clinical importance of this protein in lung carcinogenesis.
In this report, we examined UHRF1 expression using 56 US and 322 Japanese lung cancer cases by immunohistochemical analysis and found that expression of UHRF1 was significantly up-regulated in almost all histological types of lung cancers, especially in non-ADCs. The expression of UHRF1 was associated with poor prognosis and several other clinicopathological characteristics of the lung cancer patients. As UHRF1 was specifically expressed in cancer cells and detectable in approximately half of lung cancer cases in an early pathological stage, UHRF1 could be a novel diagnostic marker for lung cancer.