Does the primary tumor site in stage I extranodal natural killer/T-cell lymphoma matter?

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.

DTX3L is upregulated in glioma and is associated with glioma progression.

Gliomas are the most common primary brain tumors of the central nervous system (CNS). Due to the poor prognosis of glioma patients, it is urgent to develop more effective therapies. Deltex-3-like (DTX3L), also known as B-lymphoma and BAL-associated protein (BBAP), has been reported to play an important role in the progression of many tumors. This study aimed to investigate the clinical significance and biological function of DTX3L in human glioma. Clinically, the protein expression level of DTX3L is increased in glioma tissues compared with that observed in normal brain tissues. Immunohistochemical analysis demonstrated that DTX3L was highly expressed in the glioma tissues and its level was correlated with the grade of malignancy. Multivariate analysis revealed the association between high expression of DTX3L and the poor prognosis of glioma patients. In addition, knockdown of DTX3L by siRNA transfection increased glioma cell apoptosis. Moreover, suppression of DTX3L expression was shown to significantly inhibit the migration and invasion of glioma cells. These data indicate that DTX3L plays an important role in the pathogenic process of glioma, suggesting that DTX3L could be a potential prognostic biomarker for glioma.

High expression of PIWIL2 promotes tumor cell proliferation, migration and predicts a poor prognosis in glioma.

Piwi-like RNA-mediated gene silencing 2 (PIWIL2), has been reported as an oncogene tightly associated with the genesis and progression of various malignancies. Nevertheless, the function of the PIWIL2 protein in human gliomas has not yet been clarified. In this study, we sought to investigate the clinical significance of PIWIL2 expression and reveal its function in the pathological process of gliomas. Through western blot and immunohistochemical analyses we found that PIWIL2 was overexpressed in glioma tissues. Moreover, the expression level of PIWIL2 was also significantly correlated with the WHO grades of human gliomas and Ki-67 expression. Kaplan­Meier curves indicated that PIWIL2 was a prognostic factor for the survival of glioma patients and a high expression of PIWIL2 was correlated with a poor prognosis. In vitro, knockdown of PIWIL2 in glioma cells was shown to induce cell cycle arrest and increase apoptosis. Furthermore, silencing of PIWIL2 expression also obviously suppressed the migration of glioma cells. All the results demonstrated that PIWIL2 plays a significant role in the pathogenesis of human gliomas and may be used as a potential diagnostic marker and a therapeutic target of glioma in the future.

Silencing of OTUB1 inhibits migration of human glioma cells in vitro.

OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0.05). Moreover, Kaplan-Meier curve also indicated that high expression of OTUB1 was correlated with a poor prognosis. In vitro, silencing OTUB1 retarded the migration ability of glioma cells. Knockdown of OTUB1 increases epithelial-mesenchymal transition-related protein E-cadherin expression, but decreases simultaneously the expression of vimentin and snail. Furthermore, down-regulated expression of OTUB1 also resulted in decreased expression of some extracellular matrix degradation-related proteins, such as matrix metallopeptidase (MMP)2 and MMP9. All results suggested that OTUB1 was a valuable marker in the pathogenesis of human gliomas and could be used as a novel biomarker for glioma therapy in the future.

IGFBP6 Regulates Cell Apoptosis and Migration in Glioma.

The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.

Knockdown of DIXDC1 Inhibits the Proliferation and Migration of Human Glioma Cells.

DIX domain containing 1 (DIXDC1), the human homolog of coiled-coil-DIX1 (Ccd1), is a positive regulator of Wnt signaling pathway. Recently, it was found to act as a candidate oncogene in colon cancer, non-small-cell lung cancer, and gastric cancer. In this study, we aimed to investigate the clinical significance of DIXDC1 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that DIXDC1 was overexpressed in glioma tissues and glioma cell lines. The expression level of DIXDC1 was evidently linked to glioma pathological grade and Ki-67 expression. Kaplan-Meier curve showed that high expression of DIXDC1 may lead to poor outcome of glioma patients. Serum starvation and refeeding assay indicated that the expression of DIXDC1 was associated with cell cycle. To determine whether DIXDC1 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with interfering RNA-targeting DIXDC1; investigated cell proliferation with Cell Counting Kit (CCK)-8, flow cytometry assays, and colony formation analyses; and investigated cell migration with wound healing assays and transwell assays. According to our data, knockdown of DIXDC1 significantly inhibited proliferation and migration of glioma cells. These data implied that DIXDC1 might participate in the development of glioma, suggesting that DIXDC1 can become a potential therapeutic strategy for glioma.