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Extranodal NK/T-cell lymphoma (ENKTL), nasal type is an aggressive lymphoma characterized by rapid clinical progression, an unfavorable prognosis, and a short survival time. This study aimed to investigate the correlations of c-MYC protein expression, gene rearrangement, and gene copy number with the prognosis of ENKTL. Immunohistochemistry for CD20, CD3, CD56, TIA-1, Ki-67, and c-MYC were performed using tissue sections from 68 patients diagnosed with ENKTL. In situ hybridization was performed to detect Epstein-Barr virus (EBV)-encoded small RNA (EBER). c-MYC genetic alterations (located on chromosome 8q24) were detected using fluorescence in situ hybridization. Sixty patients with nasopharyngeal mucosa lymphadenosis were selected as a normal control group for the c-MYC gene and protein. Immunophenotypically, CD3 and TIA-1 were positive in all patients, CD56 was positive in 54 patients (79.4%), and CD20 was negative in all patients. A Ki-67 proliferation index of > 50% was observed in 94.1% of patients (64/68). In situ hybridization for EBER was positive in all patients. The c-MYC positive expression rate (> 40% of tumor cells with nuclear staining regarded as positive) in patients with ENKTL was 50% (34/68), which was significantly higher than that in patients with nasopharyngeal mucosa lymphadenosis (0%, 0/60; p < 0.05). Treatment efficacy was poor in patients with high c-MYC protein expression ( p < 0.05). Genetically, c-MYC rearrangements were not detected in any patients, but 26.5% (18/68) had increased c-MYC copy numbers. The gain of c-MYC copy numbers was positively correlated with c-MYC protein expression ( p < 0.05). Kaplan-Meier analysis illustrated that overall survival was significantly shorter in the c-MYC-positive group than in the c-MYC-negative group ( p < 0.05). Gain of c-MYC copy numbers was not associated with prognosis ( p > 0.05). Multivariate Cox regression analysis further confirmed that clinical stage and c-MYC positivity were independent prognostic factors in patients with ENKTL. The abnormal expression of c-MYC may play an important role in the development and progression of ENKTL and influence the prognosis of patients. [ABSTRACT FROM AUTHOR]

In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence ( P < 0.05). P300 expression was correlated with COX-2 expression ( P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival ( P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify prognostic autophagy‐related genes and assess the ability of these genes to predict clinical outcomes in oral squamous cell carcinoma (OSCC). Subjects and methods: The details of the human autophagy‐related genes were obtained from the Human Autophagy Database. The Cancer Genome Atlas database was used to obtain the gene expression profiles and clinical data of patients. Prediction of biological functions of differentially expressed genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Prognosis‐related genes were identified by Cox regression analysis, and the coefficient was applied to construct a prognostic risk score model. The median of the risk score was applied to distinguish between high‐ and low‐risk groups. The Gene Expression Omnibus database, qRT‐PCR and immunohistochemistry were used to validate the expression of key genes. Results: KEGG analyses revealed that differentially expressed genes were mainly enriched in autophagy‐related pathways and virus infection. BAK1, BID, NKX2‐3 and SPHK1 were identified. The risk score model showed that the high‐risk score had poorer overall survival (Kaplan‐Meier analysis, p = 1.79 × 10–7). SPHK1 was upregulated in OSCC tissues and cells, and NXK2‐3 was downregulated. Conclusions: Autophagy‐related gene expression profiles may be a potential biomarker for OSCC prognosis. [ABSTRACT FROM AUTHOR]

Pituitary tumor transforming gene-1 (PTTG1) is a novel oncogene and overexpressed in a wide variety of human cancers. However, the clinical and prognostic significance of PTTG1 in non-small cell lung cancer (NSCLC) is still unknown. The expression status of PTTG1 in NSCLC at the publicly available GEO databases ( GSE19804 ) was observed. The mRNA and protein expression of PTTG1 in NSCLC tissues and cell lines was detected by qRT-PCR and Western blot, and the association between PTTG1 expression and clinicopathological factors was analyzed by immunohistochemistry. In our Results, PTTG1 was one of genes overexpressed in NCSLC samples compared with paired adjacent normal lung samples in microarray data (GSE19804). PTTG1 mRNA and protein expressions were increased in NSCLC tissues and cell lines. PTTG1 protein expression was correlated with malignant status and poor prognosis of NSCLC patients. In conclusion, PTTG1 is correlated with NSCLC progression and as an independent poor prognostic factor in NSCLC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p < 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p = 0.038), N (p = 0.020) and TNM stage (p = 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p = 0.002) and T (p = 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis. [ABSTRACT FROM AUTHOR]

Background CDK4 is a protein kinase in the CDK family important for G1/S phase cell cycle progression. However, the roles and molecular mechanisms of CDK4 triggering nasopharynx carcinogenesis are still unclear. Methods Lentiviral-vector mediated shRNA was used to suppress CDK4 expression and examine its molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC) cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Results In this investigation, we knocked down CDK4 expression and observed that NPC cell growth and cell cycle progression were significantly blocked by suppressing expression of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found that reduced CDK4 expression elevated the expression of let-7c, a tumor-suppressive miRNA modulated by E2F1. We found that let-7c was markedly downregulated in NPC tissues compared to NPs and suppressed cell growth and cell cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein was observed to be overexpressed in NPC tissues and could be considered an unfavorable prognosis factor for NPC patients although its independent prognostic value did not reach statistical significance (p = 0.087). Conclusions Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by p15/p16/CDK4/E2F1 feedback signaling in NPC. [ABSTRACT FROM AUTHOR]

Background: CDK4 is a protein kinase in the CDK family important for G1/S phase cell cycle progression. However, the roles and molecular mechanisms of CDK4 triggering nasopharynx carcinogenesis are still unclear. Methods: Lentiviral-vector mediated shRNA was used to suppress CDK4 expression and examine its molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC) cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Results: In this investigation, we knocked down CDK4 expression and observed that NPC cell growth and cell cycle progression were significantly blocked by suppressing expression of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found that reduced CDK4 expression elevated the expression of let-7c, a tumor-suppressive miRNA modulated by E2F1. We found that let-7c was markedly downregulated in NPC tissues compared to NPs and suppressed cell growth and cell cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein was observed to be overexpressed in NPC tissues and could be considered an unfavorable prognosis factor for NPC patients although its independent prognostic value did not reach statistical significance (p = 0.087). Conclusions: Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by p15/p16/CDK4/E2F1 feedback signaling in NPC. [ABSTRACT FROM AUTHOR]

Aims To examine, in nasopharyngeal carcinoma ( NPC), the correlation of Krüppel-like factor 4 ( KLF4) expression with clinicopathological features including patient prognosis. Methods and results Using real-time PCR and immunohistochemistry, expression of KLF4 m RNA and protein was examined in NPC and nasopharyngeal tissues. The relationship of KLF4 expression levels with clinical features and prognosis of NPC patients was analysed. m RNA expression was markedly lower in NPC than in the nasopharyngeal tissues. Using immunohistochemistry, staining for KLF4 protein was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells, but decreased cytoplasmic expression was observed in atypical hyperplasia and NPC samples compared to normal and squamous epithelium samples ( P < 0.001). In addition, levels of cytoplasmic KLF4 protein were correlated inversely with the nodal (N) status (T NM classification; P = 0.002) and overall clinical stage ( P < 0.001) of NPC patients. Patients with NPC showing lower cytoplasmic KLF4 expression had a significantly shorter overall survival time than those with high NPC KLF4 expression. Multivariate analysis suggested that the level of KLF4 expression was an independent prognostic indicator ( P = 0.008) for NPC survival. Conclusion Low levels of cytoplasmic KLF4 expression are a potentially unfavourable prognostic factor for patients with NPC. [ABSTRACT FROM AUTHOR]

Expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) and its significance has been demonstrated in some cancer cells in recent clinical studies. However, the role of tumor MCP-1 and CCR2 expression in non-small cell lung cancer (NSCLC) remains unknown. The aim of the present study was to investigate the prognostic significance of MCP-1 and CCR2 expression in NSCLC cells. The relationship between MCP-1 and CCR2 expression in NSCLC cancer cells was examined by immunohistochemical staining of surgical specimens from 134 patients. Sixty-five of these patients had follow-up records. Kaplan-Meier analysis and Cox regression model were used to assess overall survival according to the presence or absence of MCP-1 and CCR2 expression in tumor cells. MCP-1 was detected in cancer cells of 107 NSCLC (79.9 %) and CCR2 was detected in cancer cells of 39 NSCLC (29.1 %). MCP-1 expression was correlated with sex, smoking habits, histology, and tumor size. Presence of MCP-1 in tumor cells was associated with better overall survival ( P = 0.018). By multivariate analysis, MCP-1 expression in cancer cells showed an independent prognostic factor for overall survival ( P = 0.002, hazard ratio [HR] = 0.256, 95 % confidence interval [CI] = 0.106-0.616). There was no significant relationship between CCR2 expression in tumor cells and clinical and pathological characteristics. Also, no significant positive correlation between MCP-1 and CCR2 expression was revealed by Spearman correlation analysis. Our data indicate that MCP-1 is overexpressed in NSCLC cells. Its expression in cancer cells is associated with better survival in NSCLC patients. [ABSTRACT FROM AUTHOR]