High CTLA-4 expression correlates with poor prognosis in thymoma patients

Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. In this study, we assessed the expression of CTLA-4 both at mRNA and protein levels in paraffin embedded-tissues from patients with thymomas. Furthermore, we evaluated the relationship between CTLA-4 expression and the clinical-pathologic characteristics and prognosis in patients with thymomas. Sixty-eight patients with median age corresponding to 62 years were included in this analysis. Thymomas were classified accordingly to the WHO and Masaoka-Koga for histochemical analysis and for prognostic significance. A statistical difference was found between CTLA-4 mRNA levels in human normal thymus compared with thymoma specimens. CTLA-4 expression was statistically found to progressively increase in A, B1, B2, AB and it was maximal in B3 thymomas. According to Masaoka-Koga pathological classification, CTLA-4 expression was lower in I, IIA and IIB, and higher in invasive III and IV stages. By confocal microscopy analysis we identified the expression of CTLA-4 both in tumor cells and in CD45+ tumor-infiltrating leukocytes, mainly in B3 and AB thymomas. Finally, CTLA-4 overexpression significantly correlates with reduced overall survival in thymoma patients and in atypical thymoma subgroup, suggesting that it represents a negative prognostic factor

Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma

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Expression of Human Leukocyte Antigen G is associated with Prognosis in Nasopharyngeal Carcinoma

Human leukocyte antigen G (HLA-G) has multiple immune regulatory functions including the induction of immune tolerance in malignancies. The roles of HLA-G have not been investigated in nasopharyngeal carcinoma (NPC). This study is aimed to evaluate the role of HLA-G as prognostic factor for NPC patients as well as its role in the immune regulation. Western assays showed high HLA-G expression in NPC cell lines, but low in the immortalized nasopharyngeal epithelial cell line NP69. HLA-G protein was further detected in 79.2% of 552 NPC specimens with immunohistochemistry (IHC), but not in normal nasopharyngeal epithelium tissue. Moreover, high expression of HLA-G predicted poor survival of NPC patients and positively correlated with tumor N classification and recurrence or metastasis. Multivariate analysis indicated that HLA-G was an independent and unfavorable prognostic factor. Furthermore, the presence of CD68+macrophages and IL-10 were also examined, which are two prognostic markers of NPC and important factors for regulating immune surveillance. The correlations of HLA-G with these two immune factors were revealed in NPC tissues. Taken together, our results suggest that HLA-G is an independent biomarker for NPC prognosis, and HLA-G might contribute to NPC progression, which might jointly regulate immune surveillance in NPC together with macrophages and IL-10

Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment

Current Management Strategy of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is an unique head and neck cancer. It is common among the southern Chinese and is closely associated with the Epstein Barr virus (EBV). To diagnose the disease in its early stage is infrequent as the symptoms are usually trivial and patients only present in late stages. Testing the blood for elevated EBV DNA has now become a screening test for the high risk group of patients, aiming to diagnose the disease in its early stages. Imaging studies, positron emission tomography scans in addition to clinical examination provide information on the extent of the disease. The confirmation of the disease still depends on endoscopic examination and biopsy. Radiotherapy with or without chemotherapy has been the primary treatment modality. The application of intensity modulated radiotherapy and the use of concomitant chemoradiation have improved the control of nasopharyngeal carcinoma together with the reduction of long term side effects. The early detection of residual or recurrence tumor in the neck or at the primary site has allowed delivery of salvage treatment. The choice of the optimal surgical salvage, either for neck disease or primary tumor depends on the extent of the residual or recurrent disease. The outcome of these patients have improved with the application of the appropriate surgical salvage

Minimally invasive treatment of oligometastasis in the liver in recurrent nasopharyngeal carcinoma

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Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (<it>EIF4G1</it>) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including patients' survival time.</p> <p>Methods</p> <p>Using real-time PCR, we detected the expression of <it>EIF4G1 </it>in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. <it>EIF4G1 </it>protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of <it>EIF4G1 </it>on cell invasion and tumorigenesis were investigated.</p> <p>Results</p> <p>The expression levels of <it>EIF4G1 </it>mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (<it>P </it>< 0.001). Immunohistochemical analysis revealed that the expression of <it>EIF4G1 </it>protein was higher in NPC tissues than that in the nasopharyngeal tissues (<it>P </it>< 0.001). In addition, the levels of <it>EIF4G1 </it>protein in tumors were positively correlated with tumor T classification (<it>P </it>= 0.039), lymph node involvement (N classification, <it>P </it>= 0.008), and the clinical stages (<it>P </it>= 0.003) of NPC patients. Patients with higher <it>EIF4G</it>1 expression had shorter overall survival time (<it>P </it>= 0.019). Multivariate analysis showed that <it>EIF4G1 </it>expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of <it>EIF4G1 </it>not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed <it>in vivo </it>xenograft tumor growth.</p> <p>Conclusion</p> <p>Our data suggest that <it>EIF4G1 </it>can serve as a biomarker for the prognosis of NPC patients.</p

Biomarkers in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in certain areas of Southern China, Southeastern Asia and Northern Africa. Currently, evaluation of NPC prognosis is mainly based on the tumor-node-metastasis (TNM) staging system. However, NPC patients with the same clinical stage often present different clinical courses, suggesting that the TNM staging is insufficient to predict prognosis of this disease. Therefore, it is important to find molecular biomarkers, which can help clinicians to identify NPC patients with worse prognosis and develop therapeutic interventions in NPC patients. This thesis presents the identification and investigation of mechanism of several novel markers in NPC. In the first paper, Caveolin-1 (Cav-1), a major structural component of caveolae, and CD147 (also known as extracellular matrix metalloproteinase inducer, EMMPRIN), a glycoprotein, were found to be overexpressed in NPC. Both Cav-1 and CD147 expression levels correlated significantly with metastasis and poor prognosis of NPC patients. Further studies revealed that Cav-1 and CD147 enhance NPC cell migration, which is associated with MMP-3 and MMP-11 (active) secretion. The role of microRNA-155 (miR-155) is associated with oncogenesis of several human tumors. In the second paper, miR-155 was found to be upregulated in NPC cell lines and clinical samples. EBV encoded LMP1 and LMP2A could further enhance the expression of miR-155 in NPC CNE1 and TW03 cells. JMJD1A was identified as a direct target of miR-155 in NPC. Downregulation of JMJD1A was significantly correlated with N stage of the TNM classification, a lower five-year survival rate, and a lower five-year disease-free survival rate of NPC patients. Spleen tyrosine kinase (Syk) is a nonreceptor tyrosine kinase and often aberrantly expressed in human cancers. In the third paper, high expression of Syk was detected in 24% of NPC cases. High expression of Syk, resulted partly from LMP2A expression in NPC, is associated with tumor recurrence and poor prognosis of NPC patients. Human chromosome 3 (Chr. 3) contains clusters of tumor suppressor genes (TSGs) involved in many cancer types. In the fourth paper, using Not I Chr. 3 microarray, ten candidate TSGs were found in NPC. Among them, the CpG island in the promoter region of Wingless-type Mouse mammary tumor virus integration site family, member 7A (WNT7a) and the intron 1 region of Integrin α9 (ITGA9) were confirmed to be hypermethylated in NPC by bisulfite sequencing and methylation specific PCR. Demethylating agent 5-aza-2′-deoxycytidine (5-aza-CdR) treatment could restore the expression of WNT7a and ITGA9 in NPC cell lines. Furthermore, WNT7a and ITGA9 were downregulated in NPC clinical samples. As both proteins execute significant functions related to the tumor cell biology, the potential of WNT7a and ITGA9 as diagnosis or therapeutic targets for NPC should be considered