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The ubiquitin-proteasome pathway is an important protein degradation regulatory system in cells. This pathway is also a reversible process that is strictly regulated, and the regulation of deubiquitinating enzymes (DUBs) represents an important facet of the process. Ovarian tumor-associated proteases domain-containing proteins (OTUDs), as a subfamily within the DUB family, serve an important role in regulatory mechanisms of several biological processes, through the regulation of gene transcription, cell cycle, immune response, inflammation and tumor growth processes, and may be important in the diagnosis of various diseases and constitute novel drug targets. However, the role of OTUDs in non-small-cell lung cancer (NSCLC) has not been fully elucidated. In the present study, the Oncomine database was used to examine gene expression in NSCLC, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results indicated that high mRNA expression levels of OTUD1, OTUD3, OTUD4 and putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 were associated with improved prognosis in all NSCLC and adenocarcinoma, but not in squamous cell carcinoma. By contrast, high expression levels of OTUD2 mRNA were associated with poorer overall survival in patients with NSCLC. These data suggested that these OTUD isozymes may be a potential drug target for NSCLC. [ABSTRACT FROM AUTHOR]

The role of radiotherapy (RT) in the treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is unclear. In the present study, a retrospective analysis of 63 patients with PMLBCL treated with or without RT was performed to evaluate the role of RT. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. After chemotherapy, 35 patients received RT, and RT was found to be associated with significantly improved 5-year overall survival (OS) (87 vs. 58%; P=0.001) and 5-year progression-free survival (PFS) (75 vs. 39%; P=0.001) rates compared with patients without RT. The subgroup analysis on 35 patients who received rituximab plus chemotherapy showed that RT did not improve the 5-year OS (88 vs. 92%; P=0.814) or the 5-year PFS (78 vs. 65%; P=0.511) rates compared with patients without RT. On multivariate analysis, RT and the addition of rituximab were predictive of increased OS [RT: Hazard ratio (HR), 0.157; P=0.018; rituximab: HR, 0.156; P=0.009] and PFS (RT: HR 0.111, P=0.001; Rituximab: HR 0.231, P=0.002) rates. However, the role of RT in PMLBCL in the rituximab era is unclear. Further investigation of the role of RT in the era of targeted therapy is required. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common bone malignancy, and is particularly prevalent in children and adolescents. OS is an aggressive tumor with a tendency to metastasize and invade to para-carcinoma tissues. The primary treatment for this tumor is a combination of surgery and chemotherapy. However, the prognosis remains poor due to chemoresistance and early metastasis. Osteopontin (OPN), a multifunctional secreted protein, has emerged as an important potential biomarker for diagnosing and treating cancer. The overexpression of OPN has been found in numerous malignant tumors, including breast, lung, gastric and ovarian cancer, as well as melanoma. Recent studies have suggested that OPN may provide an important function in the diagnosis and treatment of OS. The present review summarizes current knowledge and progress in understanding the potential role of OPN as a biomarker in OS. [ABSTRACT FROM AUTHOR]

The high mobility group A1 (HMGA1) protein is associated with poor prognosis in patients with a wide range of cancers. However, the affect of HMGA1 on the risk of mortality from breast cancer (BC) has not been fully characterized. In the present retrospective multiple center study, the HMGA1 expression level was determined by performing immunohistochemistry on surgical tissue samples of 273 BC specimens from the Second Affiliated Hospital of Zhejiang University (Zhejiang, China) and 310 BCs from the National Engineering Center for Biochip (Shanghai, China). Kaplan-Meier analysis and Cox proportional hazard model were employed to analyze the survivability. HMGA1 expression was significantly associated with tumor histological degree and body mass index (BMI). However, HMGA1 expression showed no prognostic value in patients with BC. Combined evaluation of HMGA1 expression and high BMI (≥24 kg/m2) predicted worse overall survival of BC. Therefore, HMGA1 and BMI were considered to serve synergistic roles in the development and progression of BC, and combined evaluation of HMGA1 expression and high BMI may be an effective marker in predicting poor prognosis of BC patients. [ABSTRACT FROM AUTHOR]

To improve the understanding of lymphoma associated hemophagocytic syndrome (LAHS) and find an effective treatment for this fatal disease, 57 patients with LAHS were retrospectively reviewed. The most common histopathological type was extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) (45.61%). Patients with B-cell LAHS were significantly older (P<0.001), and exhibited a higher triglyceride level (P=0.012), lower serum ferritin level (P=0.014) and lower plasma Epstein-Barr virus DNA (P<0.001) compared with patients with T/NK-cell LAHS. The median survival time of all patients was 43 days, and patients with B-cell (n=14) and T/NK-cell (n=43) LAHS had a median survival time of 55 and 40 days, respectively (P=0.797). Compared with patients who were treated based on HLH-2004 protocols combined with multidrug chemotherapy, those without chemotherapy had a reduced prognosis (P=0.002). The patients that underwent hematopoietic stem cell transplantation (HSCT) following chemotherapy had a significantly improved overall survival (OS) compared with patients that did not undergo HSCT (P=0.001). Patients with B-cell LAHS treated with rituximab (P=0.015) and patients with ENKL treated with L-asparaginase/pegaspargase (L-asp/peg) (P=0.009) had an improved prognosis compared with patients not treated with these drugs. In the T/NK-cell LAHS group, patients treated with chemotherapy containing gemcitabine did not exhibit an improved OS compared with those not treated with gemcitabine (P=0.326). Furthermore, multivariate analysis demonstrated that long diagnosis time and poor performance status were independent prognosis factors for all patients with LAHS. The present study indicated that survival time does not differ between patients with B-cell LAHS and patients with T/NK-cell LAHS. Early diagnosis and appropriate immunochemotherapy plus HSCT are essential to achieve improved outcomes. The outcome of patients with B-cell LAHS may be significantly improved following treatment with rituximab. L-asp/peg-containing regimens are promising treatments for patients with NK/T-cell LAHS. [ABSTRACT FROM AUTHOR]

Primary pulmonary mucinous adenocarcinoma (PPMA) is an uncommon subtype of lung adenocarcinoma. The present study attempted to clarify the diagnosis, clinicopathological characteristics, and pathologic significance of epithelial growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations and the prognosis of PPMA. A total of 29 patients with PPMA from among 1,469 surgically resected patients with lung adenocarcinoma were enrolled. All of the tumours expressed CK7 and 5 cases exhibited co-expression with CK20. A total of 8 cases expressed EGFR, 14 cases expressed P53 and 2 cases expressed CEA. The majority of mucinous adenocarcinomas expressed thyroid transcription factor 1, Napsin A, Villin and Cam5.2 proteins. KRAS mutations were observed in 62% of patients and were more prevalent in the lower lung lobe and in patients with invasive mucinous adenocarcinoma. A total of 2 cases exhibited an EGFR mutation, and the co-mutation of KRAS and EGFR was only detected in 1 case. The relapse-free and overall survival rates at 5 years were 70.4, and 81.5%, respectively. The results may assist to identify a molecular target and supply important information for a therapeutic strategy for patients with PPMA. [ABSTRACT FROM AUTHOR]

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma. [ABSTRACT FROM AUTHOR]

Although the correlation between glypican-5 (GPC5) and lung cancer is well known, the effect of GPC5 expression on non-small cell lung cancer (NSCLC) survival remains to be determined. In the present study, GPC5 expression in A549, H3255, and SPC-A1 NSCLC cell lines was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. GPC5 mRNA and protein expression levels were found to be higher in A549 and H3255 cells compared with SPC-A1 cells. The role of GPC5 in NSCLC cell migration was evaluated in vitro by shRNA-mediated knockdown or the overexpression of GPC5 through scratch and transwell assays. The mean migration rates of cancer cells transfected with pRNAT-shRNA-GPC5-1 were reduced compared with the controls in A549 (P<0.001) and H3255 (P=0.001), while the migration rate of SPC-A1 with GPC5 overexpression was higher than that of the control (P=0.001). The downregulation of GPC5 impeded the transmigration of A549 and H3255 while the upregulation of GPC5 expression promoted the transmembrane invasion of SPC-A1. Furthermore, a panel of formalin-fixed paraffin-embedded NSCLC tissues from 127 patients undergoing curative resection (stages I, II and III) between January, 2003 and December, 2008 were obtained in order to investigate the correlation between GPC5 expression and clinicopathological factors using immunohistochemical methods. The results demonstrated that high GPC5 expression levels in NSCLC were associated with respiratory symptoms in lung cancer diagnosis, poor differentiation, vascular invasion, regional lymph node metastasis and a higher TNM stage. Using the Kaplan-Meier method, NSCLC patients with high levels of GPC5 expression demonstrated a significantly shorter overall survival time compared with those with low GPC5 expression levels (median postsurgical survival time: 14.0 months vs. 59.0 months, P=0.001). GPC5 expression was also identified as an independent prognostic factor by Cox regression analysis [adjusted hazard ratio: 2.18; 95% confidence interval (CI): 1.35-3.52; P=0.001]. This study suggested that increased levels of GPC5 expression are a poor prognostic marker for NSCLC. [ABSTRACT FROM AUTHOR]