Identifying Thymic Masses By Using RTE Related Biomarkers

Objective:As a common type of anterior mediastinal tumors,thymoma should be accurately diagnosed and surgically removed as soon as possible because of its malignant biological behavior and the capacity of causing myasthenia gravis.Given that thymopoiesis state can be assessed by RTEs markers in peripheral blood T cells,it is an efficient and feasible way to distinguish thymoma from the various anterior mediastinal tumors by detecting RTEs or RTEs markers.It has been recently reported that RTEs,not other mature peripheral blood T cells,produce the cytokine interleukin8(IL-8/CXCL8)and that IL-8 may identify RTEs that are more recently produced by intratumorous thymopoiesis in adults,as well as in babies ~1-~4.Our study is to examine the cytokine interleukin-8(IL-8)as a new biomarker for identifying thymoma from other anterior mediastinal tumors.Methods:All patients in this study underwent surgical resection for anterior mediastinal tumors,including thymoma,thymic cyst,thymic hyperplasia,thymic carcinoma,teratoma and lymphoma,between December 2015 and March 2019 in the Thoracic Surgery Department,Zhongshan Hospital,Fudan University(Shanghai,China).Flow cytometry was used to separate the CD4~+and CD8~+na?ve T cells and IL-8 proportion in the peripheral blood mononuclear cells after PMA and ionomycin stimulation for 6 hours at 37°C in TCM medium containing 10%FBS.Clinical significance was assessed between IL-8 proportion and clinicopathological features in thymoma patients.In the follow-up process,we also observed a thymoma patient's tumor recurrence on the CT image as well as with the IL-8 at 3 months after first surgical resection.Results:Potent intratumorous thymopoiesis can be observed in thymoma and thymic hyperplasia patients rather than patients with other anterior mediastinal tumors.Intratumorous thymopoiesis can be successfully assessed in peripheral blood samples on the basis of RTE surface markers like CD31,though lacking accuracy.The IL-8proportion was markedly elevated in thymoma and thymic hyperplasia patients when compared with that in thymic cyst,thymic carcinoma,teratoma and lymphoma patients.For thymoma and thymic hyperplasia,the diagnostic sensitivity of IL-8 proportion in CD4~+and CD8~+na?ve T cells was both 100%,while the specificity was 96.77%and93.55%,respectively.Additionally,area under curve(AUC)of IL-8-producing CD4~+na?ve T cells was 0.98 and that of IL-8-producing CD8~+na?ve T cells was 0.97.Thymoma patients with Masaoka stage III and IV,or with WHO type B2 and B3thymoma,exhibited higher IL-8 proportion than patients with Masaoka stage I and II,or with WHO type A,AB,and B1 thymoma,while thymoma patients with or without myasthenia gravis exhibited the similar IL-8 proportion.Furthermore,IL-8 proportion was dramatically decreased in thymoma and thymic hyperplasia patients 3 months after thymectomy,while kept constant at a low level 3 months after surgical resection in thymic cyst,thymic carcinoma,teratoma and lymphoma patients.In the follow-up process,we observed a thymoma patient's tumor recurrence on the CT image as well as with the IL-8 higher again 13 months after first surgical resection.The patient received second surgical resection and the IL-8 decreased again 1 months after second operation.Conclusions: IL-8 can be used to accurately distinguish thymoma and thymic hyperplasia from other anterior mediastinal tumors,and may be a novel biomarker to diagnose thymoma and monitor tumor recurrence.