22 predicts poor survival in patients with early-stage non-small cell lung cancer

Currently, complete surgical resection remains the optimal treatment option for early-stage NSCLC, but even in stage I, approximately one third of patients will relapse after the initial surgery and die of metastatic recurrence within five years. 3,4 According to many randomized clinical trials, adjuvant chemotherapy is now considered the unequivocal standard treatment for resected early-stage NSCLC patients, with an estimated 4-15% survival advantage at 5 years.5-9 This survival advantage clearly indicates that only a proportion of patients benefit from adjuvant chemotherapy, while others may receive potentially toxic chemotherapy unnecessarily. Thus, it is imperative to identify novel prognostic biomarkers that can precisely predict survival in patients with early-stage NSCLC. Such advances would be helpful to stratify patients with resected NSCLC and select high-risk patients who should receive aggressive adjuvant chemotherapy. Ubiquitin-specific protease 22 (USP22) is a novel ubiquitin hydrolase that catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a co-activator. USP22 was initially identified by Glinsky et al. in a microarray-based study comparing gene expression profiles in metastatic lesions and primary tumors of prostate cancer.10 Subsequent sequence analysis revealed that USP22 is a dedicated subunit of the human Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator complex and that it functions as an activator for nuclear receptor-mediated transactivation. 11 Furthermore, USP22 has been shown to regulate proliferation and oncogenic transformation through the modulation of the transcription factors BMI, c-myc, p38 mitogenactivated protein kinase (MAPK) and others.