scholarly journals Influence of Epstein–Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guofei Feng ◽  
Yifei Xu ◽  
Ning Ma ◽  
Kaoru Midorikawa ◽  
Shinji Oikawa ◽  
...  

Abstract Background To assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). Methods A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. Results We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. Conclusions It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.

2020 ◽  
Vol 19 ◽  
pp. 153303382093577
Author(s):  
Ning Xue ◽  
Shan Xing ◽  
Weiguo Ma ◽  
Jiahe Sheng ◽  
Zhiliang Huang ◽  
...  

Introduction: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma. Materials and Methods: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques. Results: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen–negative and Epstein-Barr virus viral capsid antigen–positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen. Conclusion: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.


2005 ◽  
Vol 20 (1) ◽  
pp. 5-10 ◽  
Author(s):  
I.D. Lyronis ◽  
S. Baritaki ◽  
I. Bizakis ◽  
M. Tsardi ◽  
D.A. Spandidos

The aim of this study was to determine the possible involvement of human papillomavirus and Epstein-Barr virus in esophageal squamous cell cancer (ESCC) carcinogenesis in the Greek population. DNA was extracted from 30 ESCC and 27 normal esophageal specimens and screened for HPV type-specific or EBV infection by PCR-based assay. Seventeen out of 30 ESCC specimens (56%) were found positive for HPV DNA, of which 15 (88%) were typed as HPV-18 infected, one (5.9%) as HPV-16 infected, and one (5.9%) as infected by an HPV type different from the studied HPV-6, 11, 16, 18 and 33 subtypes. Six of the 27 normal esophageal specimens (22.2%) were positive for HPV infection, five typed as HPV-18 (83.3%) and one as HPV-16 (16.7%). All samples were negative for EBV genome detection as assessed by the PCR assay. No statistically significant correlation was found between the HPV status of the tumor samples and clinical parameters including sex, age of the patients, tobacco or alcohol use, differentiation grade of the lesions and stage of the disease. In conclusion, our findings indicate a statistically significant (p<0.001) overall association between ESCC and HPV infection, mostly related to the HPV-18 subtype, in the Greek population.


2021 ◽  
Vol 10 ◽  
Author(s):  
Frans J. Mulder ◽  
Faisal Klufah ◽  
Famke M. E. Janssen ◽  
Farzaneh Farshadpour ◽  
Stefan M. Willems ◽  
...  

ObjectiveDetermine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND).MethodsClinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis.ResultsAll oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression.ConclusionIn this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.


2005 ◽  
Vol 18 (6) ◽  
pp. 822-827 ◽  
Author(s):  
Pao-Hsien Chu ◽  
Shih-Ming Jung ◽  
Hsin-Chiung Lin ◽  
Chi-Hsiao Yeh ◽  
Hsueh-Hua Wu ◽  
...  

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