Cancer Research and Treatment

Original Articles

Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA: Ning Xue, Jian-Hua Lin, Shan Xing, Dan Liu, Shi-Bing Li, Yan-Zhen Lai, Xue-Ping Wang, Min-Jie Mao, Qian Zhong, Mu-Sheng Zeng, Wan-Li Liu; Cancer Res Treat. 2019;51(1):378-390. Published online May 29, 2018; DOI: https://doi.org/10.4143/crt.2018.070

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Purpose
The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA).
Materials and Methods
One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques.
Results
Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues.
Conclusion
Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

Citations

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Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
Chuwen Liang, Jun Kan, Jingli Wang, Wei Lu, Xiaoyan Mo, Bei Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Genetic Variants of the MIF Gene and Susceptibility of Rectal Cancer
Dongyu Chuo, Dapeng Lin, Mingdi Yin, Yuze Chen
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 55. CrossRef
microRNA-451 (miR-451) Regulates the Apoptosis of Non-Small Cell Lung Cancer Cells by Targeting Macrophage Migration Promoting Factors
Caihong Wei, Dan Guo, Huayun Pu
Journal of Biomaterials and Tissue Engineering.2021; 11(7): 1388. CrossRef

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Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study: Qiu-Yan Chen, Shao-Yan Guo, Lin-Quan Tang, Tong-Yu Lu, Bo-Lin Chen, Qi-Yu Zhong, Meng-Sha Zou, Qing-Nan Tang, Wen-Hui Chen, Shan-Shan Guo, Li-Ting Liu, Yang Li, Ling Guo, Hao-Yuan Mo, Rui Sun, Dong-Hua Luo, Chong Zhao, Ka-Jia Cao, Chao-Nan Qian, Xiang Guo, Mu-Sheng Zeng, Hai-Qiang Mai; Cancer Res Treat. 2018;50(3):861-871. Published online September 13, 2017; DOI: https://doi.org/10.4143/crt.2017.237

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Purpose
Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors.
Materials and Methods
By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above.
Results
Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant.
Conclusion
Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

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The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients: Li-Ting Liu, Qiu-Yan Chen, Lin-Quan Tang, Shan-Shan Guo, Ling Guo, Hao-Yuan Mo, Ming-Yuan Chen, Chong Zhao, Xiang Guo, Chao-Nan Qian, Mu-Sheng Zeng, Jin-Xin Bei, Jing Tan, Shuai Chen, Ming-Huang Hong, Jian-Yong Shao, Ying Sun, Jun Ma, Hai-Qiang Mai; Cancer Res Treat. 2018;50(1):19-29. Published online April 5, 2017; DOI: https://doi.org/10.4143/crt.2016.595

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test.
Results
A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ≥ 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ≥ 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ≥ 390 cells/μL and post3m-ALC ≥ 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006).
Conclusion
Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

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ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition: Dan Zong, Li Yin, Qian Zhong, Wen-jie Guo, Jian-hua Xu, Ning Jiang, Zhi-rui Lin, Man-zhi Li, Ping Han, Lin Xu, Xia He, Mu-sheng Zeng; Cancer Res Treat. 2016;48(1):334-344. Published online March 12, 2015; DOI: https://doi.org/10.4143/crt.2014.311

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). Materials and Methods The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.
Results
ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway. Conclusion Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.

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