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.