Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Identification of a seven autophagy-related gene pairs signature for the diagnosis of colorectal cancer using the RankComp algorithm.

Based on the colorectal cancer microarray sets gene expression data series (GSE) GSE10972 and GSE74602 in colon cancer and 222 autophagy-related genes, the differential signature in colorectal cancer and paracancerous tissues was analyzed by RankComp algorithm, and a signature consisting of seven autophagy-related reversal gene pairs with stable relative expression orderings (REOs) was obtained. Scoring based on these gene pairs could significantly distinguish colorectal cancer samples from adjacent noncancerous samples, with an average accuracy of 97.5% in two training sets and 90.25% in four independent validation GSE21510, GSE37182, GSE33126, and GSE18105. Scoring based on these gene pairs also accurately identifies 99.85% of colorectal cancer samples in seven other independent datasets containing a total of 1406 colorectal cancer samples.

CT-based radiomics in predicting pathological response in non-small cell lung cancer patients receiving neoadjuvant immunotherapy.

Objectives: In radiomics, high-throughput algorithms extract objective quantitative features from medical images. In this study, we evaluated CT-based radiomics features, clinical features, in-depth learning features, and a combination of features for predicting a good pathological response (GPR) in non-small cell lung cancer (NSCLC) patients receiving immunotherapy-based neoadjuvant therapy (NAT). Materials and methods: We reviewed 62 patients with NSCLC who received surgery after immunotherapy-based NAT and collected clinicopathological data and CT images before and after immunotherapy-based NAT. A series of image preprocessing was carried out on CT scanning images: tumor segmentation, conventional radiomics feature extraction, deep learning feature extraction, and normalization. Spearman correlation coefficient, principal component analysis (PCA), and least absolute shrinkage and selection operator (LASSO) were used to screen features. The pretreatment traditional radiomics combined with clinical characteristics (before_rad_cil) model and pretreatment deep learning characteristics (before_dl) model were constructed according to the data collected before treatment. The data collected after NAT created the after_rad_cil model and after_dl model. The entire model was jointly constructed by all clinical features, conventional radiomics features, and deep learning features before and after neoadjuvant treatment. Finally, according to the data obtained before and after treatment, the before_nomogram and after_nomogram were constructed. Results: In the before_rad_cil model, four traditional radiomics features ("original_shape_flatness," "wavelet hhl_firer_skewness," "wavelet hlh_firer_skewness," and "wavelet lll_glcm_correlation") and two clinical features ("gender" and "N stage") were screened out to predict a GPR. The average prediction accuracy (ACC) after modeling with k-nearest neighbor (KNN) was 0.707. In the after_rad_cil model, nine features predictive of GPR were obtained after feature screening, among which seven were traditional radiomics features: "exponential_firer_skewness," "exponential_glrlm_runentropy," "log- sigma-5-0-mm-3d_firer_kurtosis," "logarithm_skewness," "original_shape_elongation," "original_shape_brilliance," and "wavelet llh_glcm_clustershade"; two were clinical features: "after_CRP" and "after lymphocyte percentage." The ACC after modeling with support vector machine (SVM) was 0.682. The before_dl model and after_dl model were modeled by SVM, and the ACC was 0.629 and 0.603, respectively. After feature screening, the entire model was constructed by multilayer perceptron (MLP), and the ACC of the GPR was the highest, 0.805. The calibration curve showed that the predictions of the GPR by the before_nomogram and after_nomogram were in consensus with the actual GPR. Conclusion: CT-based radiomics has a good predictive ability for a GPR in NSCLC patients receiving immunotherapy-based NAT. Among the radiomics features combined with the clinicopathological information model, deep learning feature model, and the entire model, the entire model had the highest prediction accuracy.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

Importance: Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. Objective: To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. Design, Setting, and Participants: This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Exposures: Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. Main Outcomes and Measures: The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. Results: A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. Conclusions and Relevance: An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy with or without chemotherapy: Development of a nomogram based on the equivalent dose.

OBJECTIVE: The aim of this study was to establish a nomogram for predicting radiation-induced hypothyroidism (RHT) based on an equivalent dose at 2 Gy per fraction (EQD2) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy. METHODS: Two hundred forty-four eligible patients with NPC were recruited for this study. Patients' clinical factors and dose-volume parameters of the thyroid gland were retrieved from medical records and the IMRT treatment planning system, respectively. The irradiation doses were converted into EQD2 for analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis were performed to identify optimal predictors of RHT for constructing the nomogram. RESULTS: With a median follow-up of 63.0 months, the cumulative incidence rates of RHT at 3 months and 1-, 2-, 3-, 4- and 5- year after IMRT were 10.2%, 36.2%, 47.6%, 54.2%, 58.8% and 69.4%, respectively. Four independent factors for predicting RHT, including gender, age, pretreatment volume of the thyroid gland and V35Gy(3Gy) of the thyroid gland, were identified and incorporated into the nomogram. The area under the ROC curve of the nomogram was 0.747 (95% confidence interval 0.685 - 0.809). Calibration curves and DCA curves showed that the nomogram was in good agreement with the actual observations and clinical usefulness. CONCLUSIONS: The nomogram proposed in this study provides a reliable estimate of RHT risk in patients with NPC after IMRT and appears to have the potential to be a useful tool for widespread clinical applications.

Locoregional Control and Mild Late Toxicity After Reducing Target Volumes and Radiation Doses in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy (IC) Followed by Concurrent Chemoradiotherapy: 10-Year Results of a Phase 2 Study.

PURPOSE: To evaluate the long-term locoregional control, failure patterns, and late toxicity after reducing the target volume and radiation dose in patients with locoregionally advanced nasopharyngeal carcinoma patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Previously untreated patients with locoregionally advanced nasopharyngeal carcinoma were recruited into this prospective study. All patients received 2 cycles of IC followed by CCRT. The gross tumor volumes of the nasopharynx (GTVnx) and the neck lymph nodes (GTVnd) were delineated according to the post-IC tumor extension and received full therapeutic doses (68 Gy and 62-66 Gy, respectively). The primary tumor shrinkage after IC was included in the high-risk clinical target volume (CTV1) with a reduced dose of 60 Gy. The locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. RESULTS: There were 112 patients enrolled in this study. The average mean dose of post-GTVnx, post-GTVnd (left), post-GTVnd (right), post-CTV1, and post-low-risk clinical target volume (CTV2) was 75.24, 68.97, 69.16, 70.49, and 63.37 Gy, respectively. With a median follow-up of 125.95 months, the 10-year LRRFS, DMFS and OS were 89.0%, 83.3%, and 75.9%, respectively. There were 8 local recurrences and 6 regional recurrences in 12 patients. All 8 of the local recurrences were in-field; among the 6 regional recurrences, 4 were in-field, 1 was marginal, and 1 was out-field. The most common late toxicities were grade 1 to 2 subcutaneous fibrosis, hearing loss, and xerostomia. No grade 4 late toxicities were observed. CONCLUSIONS: Reduction of the target volumes according to the post-IC tumor extension and radiation dose to the post-IC tumor shrinkage could yield excellent long-term locoregional control with limited marginal and out-field recurrences and mild late toxicities.

Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage.

BACKGROUND/AIMS: Canopy homolog 2 (CNPY2) is a signature gene highly associated with tumor progression, including hepatocellular carcinoma (HCC). The presence of tumor hemorrhage (TH) implies a fast-growing and worse tumor microenvironment. We examined a possible association between CNPY2 levels and TH and evaluated their prognostic values in patients with HCC. METHODS: CNPY2 mRNA and protein levels were respectively determined in two independent cohorts of HCC specimens using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry of tissue microarrays. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. CNPY2 knockout HCC cell lines were established by the CRISPR/Cas9 gene editing system, and the functional role of CNPY2 in HCC cell proliferation and growth was examined in vitro and in vivo. RESULTS: qRT-PCR showed that CNPY2 expression was significantly higher in HCC tumor tissue than in adjacent non-tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that CNPY2 expression was significantly correlated with TH and clinicopathological features indicating worse HCC progression. The prognostic value of CNPY2 expression and TH was validated by Cox proportional hazards analyses. Furthermore, CNPY2 knockout resulted in the significant suppression of MHCC97H cell proliferation, tumor growth, and hemorrhage. Bioinformatics analysis revealed that CNPY2 was closely associated with the expression levels of 6 positive impact genes in HCC, namely, ROMO1, BOLA2, HSF1, ATG4B, ATF4, and DENR, which are implicated in the regulation of the tumor microenvironment. CONCLUSION: CNPY2 is an oncogene that plays a critical role in the progression of HCC with TH. CNPY2 could be exploited as a novel prognostic marker and potential target for therapeutic intervention in HCC.

Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

AIM: To develop a potent and safe gene therapy for esophageal cancer. METHODS: An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. CONCLUSION: The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

Pathological and MR-DWI study of the acute hepatic injury model after stem cell transplantation.

AIM: To investigate apparent diffusion coefficient (ADC) values as an indication of reconditioning of acute hepatic injury (AHI) after allogeneic mononuclear bone marrow cell (MBMC) transplantation. METHODS: Three groups were used in our study: a cell transplantation group (n = 21), transplantation control group (n = 21) and normal control group (n = 10). AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and transplantation control group for magnetic resonance diffusion-weighted imaging (MR-DWI) and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rabbits from the normal control group were used for MR-DWI examination and measurement of the mean ADC value of normal liver. RESULTS: At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group (27.14 ± 1.46 vs 69.29 ± 6.16, 22.29 ± 2.29 vs 57.00 ± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000). The mean ADC values of the cell transplantation group were significantly higher than the transplantation control group ((1.07 ± 0.07) × 10⁻³ mm²/s vs (0.69 ± 0.05) × 10⁻³ mm²/s, (1.41 ± 0.04) × 10⁻³ mm²/s vs (0.84 ± 0.06) × 10⁻³ mm²/s, (1.68 ± 0.04) × 10⁻³ mm²/s vs (0.86 ± 0.04) × 10⁻³ mm²/s, P = 0.000). The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [(1.07 ± 0.07) × 10⁻³ mm²/s vs (1.76 ± 0.03) × 10⁻³ mm²/s, (0.69 ± 0.05) × 10⁻³ mm²/s vs (1.76 ± 0.03) × 10⁻³ mm²/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different (P = 0.000). At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk (P = 0.000). However, there was no significant difference between the 2nd and 4th wk (P = 0.073 and 0.473, respectively). The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 (P = 0.000) and -0.762 (P = 0.000) in the transplantation control group. CONCLUSION: Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.

[The experimental study of magnetic resonance diffusion-weighted imaging to the treatment of acute hepatic injury with allogeneic MBMCs transplantation into liver].

OBJECTIVE: To investigate the therapeutic effect of mononuclear bone marrow cells (MBMCs) transplantation to rabbit liver with acute hepatic injury (AHI) and the feasibility that evaluated the functional recovery of acute hepatic injury model with MR-DWI. METHODS: 10 healthy rabbits were chosen to be normal control group which was only carried out MR-DWI scan of normal liver. 42 model rabbits of acute liver injury were randomly selected and divided into 2 groups:transplanted group (n = 21) and control group(n = 21). Each rabbit of the transplanted group was infused 5 ml MBMCs suspension (about containing 2 × 107 MBMCs) into its liver at multiple sites. All manipulations to each rabbit in the control group were as same as those in the transplanted group except that 5 ml of D-Hanks solution was injected instead of MBMCs suspension.7 model rabbits respectively chosen from the transplanted group and the control group were carried out MR-DWI scan and calculated the mean ADC value of the injury liver and then were killed on day 7, day 14 and day 28 of AHI establishment after transplantation. Other comparative assays were performed including: functional assay of liver, pathological examination of liver sections. RESULTS: Before MBMCs transplantation, the difference of liver function was not significant between the transplanted group and the control group. But after MBMCs transplantation, the liver functions of the transplanted group were significantly better than those of the control group at all time points tested (P < 0.05). On day 7 of AHI establishment after MBMCs transplantation, the mean ADC values of the transplanted group and the control group were significant lower than those of the normal control group (P < 0.05). The mean ADC values of the transplanted group and the control group increased to the mean ADC values of the normal control group over time. At the same time point, the mean ADC values of the transplanted group were significantly higher than those of the control group. In the transplanted group, the difference of average ADC values between any two time points were significantly (P < 0.05). In the control group, the mean ADC values on day 7 were lower than those on day 14 and day 28 (P < 0.05), the mean ADC values on day 14 were lower than those on day 28 (P = 0.417). The correlation between the average ADC value and the ALT or AST was negative (P < 0.05), the correlation between the average ADC value and the ALB was positive (P < 0.05). Along with the increase of the average ADC value, the liver function of the AHI model rabbit gradually got better. CONCLUSION: Transplantation of MBMCs promoted the recovery of liver function of AHI model rabbit. The recovery of the injury liver could be detected with observing dynamic change of its mean ADC value.

Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells.

INTRODUCTION: Cyclin D1 (D1) binds to cyclin-dependent kinases (CDK) 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H)-dione (NPCD), a novel CDK4 inhibitor, on breast cancer cell lines. METHODS: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation. RESULTS: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines. CONCLUSIONS: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of Rb by D1-CDK4/6 and decreased p27kip1 protein level may be part of the underlying mechanism.

[Expression clinical significance of nm23-H1 and vessel endothelium growth factor protein in nasopharyngeal carcinoma].

OBJECTIVE: To study the prognostic predictor for nasopharyngeal carcinoma (NPC). METHODS: The expressions of nm23-H1 and vessel endothelium growth factor (VEGF) protein were examined by immunohistochemistry S-P staining in 108 NPC tissues, the expression of nm23-H1 and VEGF protein in NPC tissues with clinical stage of NPC, radiosensitivity of tumor, survival rate of patients, relapse and metastasis of carcinoma were studied. RESULTS: The positive rate of nm23-H1 and VEGF was 48.1% and 59.3% respectively. The clinical staging, metastatic potential of lymph nodes were correlated with low-level expression of nm23-H1 protein. The patients with negative nm23-H1 expression had worse prognosis than those with positive nm23-H1 expression. The clinical staging, metastatic potential and poor sensitivity of radiotherapy were correlated with high level expression of VEGF protein. The patients with positive VEGF expression had worse prognosis than those with negative VEGF expression. The expression of nm23-H1 protein was negatively correlated with the expression of VEGF protein (r = -0.577, P < 0.05). CONCLUSIONS: The low level expression of nm23-H1 protein and the high level expression of VEGF protein may be associated with the development and poor prognosis of NPC.