| Object: Abnormal vascular structure in the microenvironment of nasopharyngeal carcinoma can lead to tumor hypoxia.Hypoxia and neovascularization are closely related to the occurrence,invasion and metastasis of NPC,and will reduce the sensitivity of the tumor to various treatments.At present,the treatment of NPC with antiangiogenic targeted drugs has become a hot topic,so it is very important to evaluate the state of hypoxia and angiogenesis in NPC.Hypoxia-inducible factor-1α has been one of the most widely used hypoxia markers in clinical practice in recent years,which,according to previous researches,can induce downstream hypoxia target gene expression and plays an important role in tumor angiogenesis,energy metabolism,invasion and metastasis.Dynamic contrast-enhanced MRI technology uses intravascular contrast agent and magnetic resonance rapid acquisition technology,which reflects angiogenic activity and capillary permeability in nasopharyngeal carcinoma tissues.The purpose of this study was to explore the correlation between imaging,pathology and clinical indicators of nasopharyngeal carcinoma to evaluate the hypoxia and angiogenesis status of the tumor,so as to provide a basis for non-invasive prediction of the efficacy of nasopharyngeal carcinoma before treatment and the formulation of individualized treatment plans.Methods: 42 newly diagnosed patients with NPC confirmed by pathology in Head and Neck Cancer Radiotherapy Department of Jiangxi Cancer Hospital from April 2018 to December 2019 were collected as subjects,including 29 males and 13 females,aged 27-76 years old with the median age 58 and the average age(53.2 ± 13.6)years.Before treatment,conventional Magnetic Resonance Imaging(MRI)and dynamic contrast-enhanced MRI(DCE-MRI)were used to obtain images,and the T1-Perfusion post-processing software of PHILIPS nebula workstation was applied to select the largest layer of the tumor and delineate the Region of interest(ROI)along the edge of the lesion(avoiding bone,necrosis,vascular and other structures)as well as to calculate several DCE-MRI parameters of tumor in region of interest such as relative enhancement(RE),maximum relative enhancement(MRE),maximum enhancement(ME),time to peak(TTP),wash in rate(WIR),wash out rate(WOR),and area under the curve(AUC).Then according to the region of interest selected by MRI,electronic fiberscope biopsy of nasopharynx was conducted to prepare pathological sections,and the diagnosis of nasopharyngeal carcinoma was confirmed by HE staining.The expression of hypoxia-inducible factor-1α(HIF-1α)in biopsy specimens was detected by immunohistochemistry.Additionally,fifteen patients with chronic nasopharyngitis were collected for comparison.The clinical stages of patients were evaluated by experienced radiologists and clinical radiation therapists.DCE-MRI parameters of nasopharyngeal carcinoma,the expression of hypoxia-inducible factor-1α,and clinical stages were analyzed to investigate correlations.Results: 1.Clinical stages Of the 42 patients with nasopharyngeal carcinoma,2 were in stage I,8 in stage II,18 in stage III,and 14 in stage IV.Among all,6 cases were in T1 stage,11 in T2,18 in T3,and 7 in T4;12 cases were in N0 stage,12 cases in N1,10 cases in N2,8 cases in N3;38 cases in M0,and 4 cases in M1.2.DCE-MRI parameters Of 42 cases of nasopharyngeal carcinoma,the DCE-MRI parameters regarding RE,MRE,ME,TTP,WIR,WOR,and AUC were(128.98 ± 9.89)%,(136.72 ± 10.14)%,(1244.03 ± 203.77),(131.76 ± 54.45)s,(21.72 ± 9.31)s-1,(1.54 ± 0.71)s-1,(298820.54 ± 112728)respectively.3.HIF-1α expression Among 42 nasopharyngeal carcinoma biopsies,24 cases were positive for HIF-1α and 18 cases were negative;15 cases of nasopharyngeal chronic inflammation were negative for HIF-1α.The difference between those two groups was statistically significant(P <0.05).4.Correlation between DCE-MRI parameters and stage of nasopharyngeal carcinoma There was no statistical significance between the DCE-MRI parameters in the 42 cases of nasopharyngeal carcinoma and the age and gender of different patients(P> 0.05).However,the RE,ME,and MRE values are related to the clinical stage(F = 3.646,P = 0.021;F = 3.204,P = 0.034,F = 3.050,P = 0.040)and the T stage(F = 6.578,P = 0.001;F = 3.540,P = 0.023;F = 4.384,P = 0.010).The differences between the groups were statistically significant(P <0.05).As clinical stage and T stage increased,the values of RE,MRE,and ME gradually increased.However,RE,ME,MRE values were not related to N stage and M stage(P> 0.05).The difference between TTP(s),WIR(s-1),WO(s-1),AUC and the clinical stage,T stage,N stage,and M stage showed no statistical significance(P> 0.05).5.Correlation between HIF-1α expression and stage of nasopharyngeal carcinoma There was no significant difference between the expression of HIF-1α and patients’ age and gender in these 42 cases(P > 0.05);however,the positive rate of HIF-1α was significantly correlated with the clinical stage and T stage.The higher the clinical stage and T stage went,the higher the positive rate of HIF-1α became;T1 was 16.7%(1/6),T2 36.4%(4/11),T3 72.2%(13/18),and T4 85.7%(6/7);stage I was 0(0/2),stage II 12.5%(1/8);stage III 55.6%(10/18),and stage IV 92.9%(13/14).The positive rate of HIF-1α was 71.9%(23/32)in 32 cases of middle and advanced nasopharyngeal carcinoma(stage Ⅲ-Ⅳ),and only 10.0%(1/10)in 10 cases of early nasopharyngeal carcinoma(stageⅠ-Ⅱ)was positive.The positive rate of HIF-1α in tumor tissue of advanced patients was significantly higher than that of early patients,and the difference showed statistical significance(P < 0.01).6.Correlation between DCE-MRI parameters and HIF-1α expression RE,ME,and MRE were positively correlated with HIF-1α expression,which was significantly higher in the HIF-1α positive group than the negative group.The difference between those two groups had statistical significance(F =5.281,P=0.027).F = 11.923,P = 0.001;F =6.228,P=0.017)while the difference between the positive and negative groups was not statistically significant(P > 0.05).Conclusion: 1.There was a good correlation between HIF-1α and the stage of nasopharyngeal cancer.The higher the stage of NPC is,the more serious the hypoxia is and the higher the positive rate of HIF-1α is.2.The values of RE,ME and MRE in DCE-MRI parameters have a good correlation with the expression of hypoxia marker HIF-l α in NPC,which can reflect the hypoxia state in the local microenvironment of the cancer in vivo.3.The values of RE,ME and MRE have a good correlation with the stage of NPC.The vascular permeability,blood perfusion and microvessel density of NPC can be reflected by the values of RE,me and MRE.These three values can be used as important parameters to evaluate the microcirculation perfusion of NPC.As a noninvasive imaging technique,DCE-MRI has certain value in the evaluation of hypoxic and angiogenic state of NPC and the prediction of curative effect. |
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