Independent Prognostic Factor For Nasopharyngeal Carcinoma Research Articles

Nomogram Based on Hemoglobin, Albumin, Lymphocyte and Platelet Score to Predict Overall Survival in Patients with T3-4N0-1 Nasopharyngeal Carcinoma.

There is still uncertainty regarding the prognosis of nasopharyngeal carcinoma (NPC) based on hemoglobin, albumin, lymphocytes, and platelets (HALP) score. The aim of this study was to build and verify a nomogram using HALP score to investigate the prognostic value of NPC and identify low-risk patients in T3-4N0-1 NPC to guide treatment options. A total of 568 NPC patients with stage T3-4N0-1M0 were recruited in the study, who were given either concurrent chemoradiotherapy (CCRT) or induction chemotherapy (IC) plus CCRT. The prognostic factors of overall survival (OS) were picked by Coxproportional hazards regression analysis to generate a nomogram, which appraised by discrimination, calibration and clinical utility.Patients were stratified according to risk scores calculated by the nomogram, and compared to the 8th TNM staging system using the Kaplan-Meier methods. Multivariate analysis showed that TNM stage, Epstein-Barr virus DNA (EBV DNA), HALP score, lactate dehydrogenase-to-albumin ratio (LAR) and systemic inflammatory response index (SIRI) were independent prognostic indicators for OS, and these factors contained in the nomogram. Thenomogramdemonstrated a significant enhancement over the 8th TNM staging system in terms of assessing OS (C-index, 0.744 vs 0.615 in the training cohort, P < 0.001; 0.757 vs 0.646 in the validation cohort, P = 0.002). Calibration curves displayed good agreement and the stratification in high-risk and low-risk groups resulted in a significant divergence of Kaplan-Meier curves for OS (P < 0.001). In addition, the decision analysis (DCA) curves confirmed satisfactory discriminability and clinical utility. The HALP score was an independent prognostic factor for NPC. The prognostic function of the nomogram for T3-4N0-1 NPC patients was more accurate compared to the 8th TNM system, facilitating personalized treatment planning.

Prognostic potential of a voxelwise invasion risk map of nasopharyngeal carcinoma based on a coordinate system of the nasopharynx.

Tumor invasion risk (TIR) is an important prognostic factor in nasopharyngeal carcinoma (NPC). We propose a novel prognostic analytic method for NPC based on a voxelwise analysis of TIR in a coordinate system of the nasopharynx. A stable nasopharynx coordinate system was constructed based on anatomical landmarks to obtain an accurate TIR profile for NPC. The coordinate system was validated by image registration of the lateral pterygoid muscle (LPM). The tumors were registered to the coordinate system through shift, scale, and rotation transformations. The voxelwise TIR map for NPC was obtained by superposition of all registered and mirrored tumor regions of interest. The minimum risk (MinR) point of the tumor region was used as an independent prognostic factor for NPC. The cutoff value was calculated with density plot and validated with restricted cubic splines (RCSs), and then the patients were divided into 2 groups for overall survival (OS) analysis. The first voxelwise TIR map of NPC was obtained based on 778 patients. The OS of patients with a low TIR was 76.8% and was 92.6% for patients with a high TIR [P<0.001; hazard ratio (HR) =1/0.45; 95% CI: 0.27-0.77; adjusted P=0.004]. Thus, patients with a low TIR had a poor prognosis, whereas patients with a high TIR had a good prognosis. The MinR may be better at grading the prognosis of patients compared to the American Joint Committee on Cancer (AJCC) staging or tumor/node (T/N) classification systems. The voxelwise TIR map provides a new method for the prognostic analysis of NPC. Potential clinical applications of voxelwise TIR mapping are clinical target volume (CTV) delineation and dose-painting for NPC.

Prior cancer history predicts the worse survival of patients with nasopharyngeal carcinoma.

Previous cancers can be observed in patients with nasopharyngeal carcinoma (NPC). However, whether prior cancer diagnosis affects survival outcomes remains unknown. This study aimed to explore the impact of prior cancer on the survival of patients with NPC. We retrospectively collected data from 666 NPC patients between 2006 and 2018. The patients in this study were divided into those without prior cancer, with prior head and neck cancer, and prior non-head and neck cancer. The demographic data and survival of these groups were then analyzed. The independent prognostic factors for NPC were determined using multivariate Cox regression analysis. We identified 25 NPC patients with prior cancer in our case series, most of whom had a history of colorectal cancer. Patients with a history of cancer were older than those without a history of cancer (p = 0.001). In the subgroup analysis stratified by the timing of prior cancer, NPC patients with prior non-head and neck cancer within 24, 36, 60, and 120months showed worse survival than patients without prior cancer (all p < 0.05). When stratified by cancer stage, stage III NPC patients with prior non-head and neck cancer showed worse survival than patients without prior cancer (p < 0.001). Prior cancer and diabetes can predict worse survival in patients with stage III NPC. This study demonstrated that prior cancer and diabetes are independent prognostic factors in patients with stage III NPC.

High SPIN4 Expression Is Linked to Advanced Nodal Status and Inferior Prognosis in Nasopharyngeal Carcinoma Patients.

Nasopharyngeal carcinoma (NPC), characterized by the infiltration of lymphocytes, is a malignancy derived from the epithelium of the nasopharynx. Despite its sensitivity to radiation and chemotherapy, NPC has a high propensity for recurrence and metastasis. Although lymph node levels have been indicated as an independent prognostic factor for NPC, there has been no precise prognostic biomarker to predict clinical outcomes for NPC before advanced disease. In the present study, we surveyed differentially expressed genes in NPC via the next-generation sequencing (NGS)-based Oncomine database and identified the spindlin family member 4 (SPIN4) gene as the most relevant to advanced nodal status. We collected 124 tumor samples from NPC patients receiving biopsy, and the expression level of SPIN4 was evaluated by immunohistochemistry. The results showed that tumors with high SPIN4 expression were significantly correlated with advanced nodal status (p < 0.001) and advanced AJCC stages (p < 0.001). High SPIN4 expression in tumor samples was an unfavorable prognostic factor for all three endpoints at the univariate level: disease-specific survival (DSS), distal metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) (all p < 0.05). High SPIN4 expression remained independently prognostic of worse DMeFS (p = 0.049) at the multivariate level. Using bioinformatics analysis, we further found that high SPIN4 level may link tight junctions to cancer cell survival. Collectively, these results imply that high SPIN4 expression is linked to an aggressive clinical course, including advanced nodal status and poor survival in NPC patients, emphasizing the promising prognostic utility of SPIN4 expression.

Expression of ANCR in nasopharyngeal carcinoma patients and its clinical significance.

Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.

Methylation-associated silencing of miR-9-1 promotes nasopharyngeal carcinoma progression and glycolysis via HK2.

Characteristically, cancer cells metabolize glucose through aerobic glycolysis, known as the Warburg effect. Accumulating evidence suggest that during cancer formation, microRNAs (miRNAs) could regulate such metabolic reprogramming. In the present study, miR‐9‐1 was identified as significantly hypermethylated in nasopharyngeal carcinoma (NPC) cell lines and clinical tissues. Ectopic expression of miR‐9‐1 inhibited NPC cell growth and glycolytic metabolism, including reduced glycolysis, by reducing lactate production, glucose uptake, cellular glucose‐6‐phosphate levels, and ATP generation in vitro and tumor proliferation in vivo. HK2 (encoding hexokinase 2) was identified as a direct target of miR‐9‐1 using luciferase reporter assays and Western blotting. In NPC cells, hypermethylation regulates miR‐9‐1 expression and inhibits HK2 translation by directly targeting its 3' untranslated region. MiR‐9‐1 overexpression markedly reduced HK2 protein levels. Restoration of HK2 expression attenuated the inhibitory effect of miR‐9‐1 on NPC cell proliferation and glycolysis. Fluorescence in situ hybridization results indicated that miR‐9‐1 expression was an independent prognostic factor in NPC. Our findings revealed the role of the miR‐9‐1/HK2 axis in the metabolic reprogramming of NPC, providing a potential therapeutic strategy for NPC.

MiR-1254 induced by NESG1 inactivates HDGF/DDX5-stimulated nuclear translocation of β-catenin and suppresses NPC metastasis

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Chinese and other Southeast Asians. We aimed to explore the precise mechanism for NESG1 in NPC for understanding the pathogenesis of NPC. Transwell, Boyden assays, and wounding healing were respectively performed for cell metastasis. The microRNA (miRNA) microarray and luciferase reporter assays were designed to clarify NESG1-modulated miRNAs and miR-1254-targeted protein. Western blotting assays examined the pathways regulated by miR-1254, the (Hepatoma-Derived Growth Factor) HDGF/DDX5 complex, and NESG1. The chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and co-immunoprecipitation (coIP) assays were used to explore the DNA-protein complex and protein-protein complex. NESG1 suppressed NPC migration and invasion via Wnt/β-catenin signaling. Further, miR-1254 was confirmed as a positive downstream modulator of NESG1 reducing metastatic abilities of NPC cells in vivo and in vitro. Transduction of HDGF significantly restored cell migration and invasion ability in miR-1254-overexpressing NPC cells. In clinical samples, miR-1254 expression was negatively correlated with HDGF and positively correlated with NESG1 expression. miR-1254 acts as an independent prognostic factor for NPC, which was induced by NESG1 to suppress NPC metastasis via inactivating Wnt/β-catenin pathway and its downstream EMT signals.

The Prognostic Value of Deficient Mismatch Repair in Stage II\u2013IVa Nasopharyngeal Carcinoma in the Era of IMRT

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II–IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1–87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.

Low-Dose Aspirin Use Significantly Improves the Survival of Late-stage NPC: A Propensity Score-Matched Cohort Study in Taiwan.

Background: Aspirin use has been associated with improved survival rates in various cancers. However, it remains unclear if aspirin confers a survival benefit on patients with nasopharyngeal carcinoma (NPC). The aim of this study was to assess the associations between aspirin use and survival in different stages of NPC. Methods: This is a 10-year retrospective cohort study of NPC patients. A total of 565 NPC patients were recruited after we performed a 1:4 propensity score match between aspirin users and non–users. Cox regression models with adjusted covariates were employed to evaluate factors that influence the survival rate of NPC patients. Results: The Kaplan-Meier analysis revealed that the overall survival (p < 0.0001) and disease-specific survival (p < 0.0001) rates of 180-day aspirin users increased. Increased survival rates were also observed in 180-day aspirin users with Stages III and IV, T, N1 and 2, and N3 categories. Cox regression models indicated that factors, including aspirin use (univariate: HR = 0.28, 95% CI = 0.14–0.55, p < 0.001; multivariate: HR = 0.23, 95% CI = 0.12–0.46, p < 0.001), were independent prognostic factors for survival. Conclusions: Aspirin use for more than 180 days is associated with an increased survival rate and is a positive independent prognostic factor in NPC.

Paranasal sinus invasion suggested T4 classification of patients of nasopharyngeal carcinoma: A two-center retrospective investigation.

To investigate the prognostic significance of paranasal sinus invasion in nasopharyngeal carcinoma (NPC) patients. Patients with NPC after intensity-modulated radiotherapy from 2010 to 2013 were identified (n = 1225). Clinical features and magnetic resonance images were analyzed. Paranasal sinus invasion was identified in 182/1225 patients (14.9%). Multivariate analysis showed that paranasal sinus invasion was an independent factor for overall survival, progression-free survival, distant metastasis-free survival, and local recurrence-free survival (P < .05 for all). T3 NPC patients with paranasal sinus invasion had a poorer prognosis than those without (P < .05), and there was no significant survival difference compared with T4 patients, regardless of involvement of inner structures (P > .05 for all). Upgrading NPC with paranasal sinus invasion to T4 disease achieved better predictive abilities. Paranasal sinus invasion is an independent prognostic factor for NPC. It may be appropriate to upgrade the T classification.

A Proposal of N Classification Based on Quantitative Metastatic Lymph Node Regions in Nasopharyngeal Carcinoma

To assess the prognostic importance of the absolute number of metastatic lymph node regions (NLR) in patients with nasopharyngeal carcinoma (NPC), and to explore the feasibility of a new N classification system based on quantitative nodal regions. Magnetic resonance imaging (MRI) scans of 358 patients with histologically diagnosed non-disseminated NPC were reviewed. Tumor characteristics regarding the 8th UICC/AJCC staging system were documented, as well as additional metastatic lymph node (LN) features including extranodal spread (ENS), central necrosis, nodal distribution and NLR. Following the 2013 consensus guideline for delineation of the neck node levels for head and neck tumors, LN regions were quantified by summing up the involved subunits of VIIa (retropharyngeal nodes), I, IIa, IIb, III, IVa, IVb, Va, Vb, Vc, VI, III, IX, X. Univariate and multivariable survival analyses were performed with Cox proportional hazards models to test the prognostic value of variables. NLR showed significant correlation to other LN characteristics and N stage by 8th UICC/AJCC system (P<0.001). Univariate analysis showed that all listed nodal variables were significantly related to overall survival (OS), distant metastasis free survival (DMFS) and disease free survival (DFS). After adjusting for clinical variables such as age, sex, treatment modality etc, multivariable models revealed that only NLR and maximum LN diameter (MLD)>6cm were significant predictors for DMFS, while T category and ENS were significant for OS; MLD>6cm, NLR and ENS were significant for DFS. Based on these variables N was then categorized into: N0, no lymph node metastasis; N1, NLR 1-3, without ENS; N2, NLR 4-9, or NLR 1-3 with ENS; N3, NLR≥10 or MLD>6cm. This classification showed good and stable concordance with DMFS, OS and DFS, compared to N staging system by 8th UICC/AJCC (Table 1). NLR, as a potential surrogate for quantitative LN tumor burden, is a predominant independent prognostic factor in NPC. Integration of quantitative nodal regions may simplify N staging and warrants further validation in future.Abstract MO_44_2892; Table 1Classification of N according to 8th edition of UICC/AJCC staging system and proposed system8th edition of N stageProposed N classificationN5y-DMFS, %5y-OS, %5y-DFS, %N5y-DMFS, %5y-OS, %5y-DFS, %N01009093.1N010093.193.1N19289.984.4N192.190.485.3N280.175.763.4N285.482.070.9N373.576.961.8N360.167.448.6Overall P<.0010.011<.001Overall P<.001<.001<.001Abbreviations: DMFS = distant metastasis free survival; OS = overall Survival; DFS = disease free survival. Open table in a new tab

Prognostic Value and Staging Classification of Lymph Nodal Necrosis in Nasopharyngeal Carcinoma after Intensity-modulated Radiation Therapy

To evaluate the prognostic value of magnetic resonance imaging (MRI)-determined lymph nodal necrosis (LNN) in patients with nasopharyngeal carcinoma (NPC) and further explored the feasibility of an N-classification system based on the 8th edition of the American Joint Committee on Cancer (AJCC) system. The MRI scans of 616 patients with newly diagnosed stage T1, 4N1, 3M0 NPC treated with definitive intensity-modulated radiotherapy (IMRT) were reviewed retrospectively. The incidence of LNN was 38.1% (235 of 616). Multivariate analysis showed that LNN was an independent prognostic predictor of distant metastasis free survival and overall survival. The survival outcomes for patients with classification N2 disease and LNN were similar to patients with classification N3 disease. Patients with classification N1 disease and LNN had similar survival outcomes as those with stage N2 disease without LNN. Patients of classification N1 disease with LNN were reclassified as classification N2, and classification N2 disease with LNN as classification N3 in the proposed N-classification system. Correlation with death and distant failure was significant, and the total difference between N1 and N3 was wider with the proposed system. The overall distribution pattern of the proposed N-classification was more equitable than that of the 8th AJCC N-classification. MRI-determined LNN is an independent prognostic factor for NPC treated by IMRT. The proposed N classification system with MRI-determined LNN based on the 8th AJCC system is powerfully predictive.

Development and validation of nomogram based on SIRI for predicting the clinical outcome in patients with nasopharyngeal carcinomas

The Systemic Inflammation Response Index (SIRI), based on peripheral lymphocyte, neutrophil, and monocyte counts, was recently investigated as a prognostic marker for several tumors. However, use of the SIRI has...

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma.

SETDB1, an H3K9‑specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non‑tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan‑Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. Invitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5‑8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

Standardized tumor volume: an independent prognostic factor in advanced nasopharyngeal carcinoma.

The study evaluated the prognostic effect of standardized tumor volume in patients with advanced nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy. Between Jan 1, 2009 and December 30, 2012, 143 patients diagnosed with NPC in UICC stage III–IVb by histopathology were enrolled in the study. These patients underwent intensity-modulated radiotherapy combined with concurrent chemotherapy. The three-dimensional images of tumor volume were reconstructed automatically by the treatment planning system. SGTVnx was calculated based on GTVnx/person’s volume. SGTVnd was calculated based on GTVnd/person’s volume. SGTVnx was significantly associated with the 5-year overall survival (OS), disease-free survival (DFS), DMFS, and LRFS rates in univariate and multivariate analyses. Although SGTVnd was associated with the 5-year OS, DFS, and DMFS rates, it was not an independent prognostic factor for LRFS. In receiver operating characteristic (ROC) curve analysis, 1.091 and 0.273 were determined as the cut-off points for SGTVnx and SGTVnd, respectively. The 5-year OS, DFS, DMFS, and LRFS rates for patients with a SGTVnx > 1.091 vs. SGTVnx ≤ 1.091 was 65.4% vs. 93.4% (P < 0.001), 65.2% vs. 94.8% (P < 0.001), 71.4% vs. 97.4% (P < 0.001), and 84.8% vs. 97.3% (P = 0.003), respectively, for SGTVnd > 0.273 vs. SGTVnd ≤ 0.273 was 70.3% vs. 96.5% (P < 0.001), 70.1% vs. 94.8% (P < 0.001), 77.5% vs. 98.2% (P < 0.001), and 88.5% vs. 96.6% (P = 0.049), respectively. UICC stage grouping, T classification, N classification, and sex were not found to be independent prognostic factors for NPC. Standardized tumor volume was an independent prognostic factor for NPC that might improve the current NPC TNM classification system and provide new clinical evidence for personalized treatment strategies.

Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis

The objective of the present study was to evaluate the role of the TGFβ/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship to NPC prognosis. NPC tissues collected from 66 NPC patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues. Immunohistochemical staining was performed to assess expression of transforming growth factor-β receptor I (TGFβRI), programmed cell death 4 (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to evaluate NPC patient overall survival (OS) and progression-free-survival (PFS). Cox regression analysis was used to estimate independent prognostic factors for NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an inhibitor of TGFβRI; expression of TGFβRI and PDCD4 in CNE2 cells was determined by western blotting. NPC tissues showed higher expression of TGFβRI and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05). The results of Kaplan-Meier analysis showed that TGFβRI-positive patients and AP-1-positive patients had shorter OS and PFS than TGFβRI-negative patients and AP-1-negative patients; additionally, PDCD4-positive patients had higher OS and PFS than PDCD4-negative patients. Cox regression analysis revealed that advanced tumor stage, overexpression of TGFβRI and AP-1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in NPC patients. Compared with the control group, expression of TGFβRI decreased and that of PDCD4 increased significantly in CNE2 cells treated with the inhibitor (all P < 0.05). These findings indicate that the TGFβ/PDCD4/AP-1 pathway may be associated with NPC development and progression. High expression of TGFβRI and AP-1 and low expression of PDCD4 may be unfavorable prognostic factors for NPC.

Prognostic value of the primary lesion apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma: a retrospective study of 541 cases.

The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10−3 mm2/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation.

High expression of sphingosine kinase 1 is associated with poor prognosis in nasopharyngeal carcinoma

It has been reported that sphingosine kinase 1 (SPHK1), an oncogenic enzyme, was involved in the development and progression of a number of human cancers. However, the role of SPHK1 in nasopharyngeal carcinoma (NPC) is largely unknown. The present study aimed to characterize the expression of SPHK1 in human NPC and evaluate its clinical significance. Real-time quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) and Western blot analyses showed that the expression of SPHK1 mRNA and protein in NPC specimens was significantly higher than that in non-tumorous nasopharyngeal mucosa biopsies. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SPHK1 in 142 archived paraffin-embedded NPC specimens. Statistical analyses revealed that high levels of SPHK1 expression were associated with the clinical stages, locoregional recurrence and distant metastasis of NPC. NPC patients with high levels of SPHK1 expression had shorter survival time, whereas those with lower levels of SPHK1 expression survived longer. Moreover, multivariate analysis suggested that SPHK1 up-regulation was an independent prognostic factor for NPC. Our results suggest for the first time that SPHK1 is involved in the development and progression of NPC, which can be used as a useful prognostic marker for NPC patients and may be an effective target for treating NPC.

The Dose of Elective Neck Irradiation as 46 Gy Is Feasible in Nasopharyngeal Carcinoma Treated by Intensity Modulated Radiation Therapy

Purpose/Objective(s): Previous research demonstrated that the primary tumor volume (PTV) could serve as an important prognostic factor in nasopharyngeal carcinoma (NPC).However, measurement of PTV by conventional manual tracing is so complicated and time consuming that it is generally not suitable for clinical practice, and also violates the simple principles which staging systems should follow. This raises the question of whether another simple method related to the tumor load exists to predict the prognosis of NPC insteadof tumor volume.Maximumprimary tumor diameter (MPTD) iswidely used in the TMN staging of head-and-neck cancers. The goal of this study was to evaluate the prognostic value of MPTD in NPC. Materials/Methods: Three hundred and thirty-three consecutive, newlydiagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD. Results: Median follow-up was 66 months (range, 2-82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD 30 mm was 62.3%; 72% and 62.9%of T2 and T3 patients had aMPTD> 30-50mm, and 83.5% of T4 patients had aMPTD> 50mm. For patients with aMPTD 30 mm,> 30-50mm and> 50mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs 58.4% (P Z 0.010), 77.5% vs 65.2% (P Z 0.013) and 83.6% vs 73.6% (P Z 0.047), respectively. In patients with aMPTD 30mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (PZ 0.172). Conclusions: Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging. Author Disclosure: Y. Chen: None. S. Liang: None. Y. Deng: None. N. Zhang: None. R. Lu: None.H. Zhao: None.H. Chen: None. S. Li: None. D. Liu: None.

MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma

BackgroundMiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC).MethodsQuantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting.ResultsMiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P < 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion.ConclusionsThe newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target.