| Thymic carcinoma(TC),originating from thymic epithelial cells,is an extremely rare thoracic malignancy.Compared with thymoma,TC has a more invasive behavior and a worse prognosis.Due to the rarity,studies on TC are limited,and the outcomes among these studies have great heterogeneity.As a result,there are many unsolved problems on TC,including the following three:(1)prognostic factors of TC remain controversial,and there is no favorable model to predict its prognosis;(2)the mechanism of TC is unknown,and there is a lack of prognostic and therapeutic molecules;(3)effective molecules to differentiate TC from thymoma and other thymic diseases are still unsettled.We designed the present study based on these three problems,aiming to provide evidence and insights into the solutions.In TC,it is well recognized that patients with advanced disease and not underwent surgery have worse prognoses.However,Masaoka system,the most commonly used staging system in thymic epithelial tumors(TETs),is considered less effective to assess TC.Besides,apart from surgery,the effectiveness of other treatments,such as radiotherapy and chemotherapy,is inconclusive.Thus,making individual decision is still difficult in TC patients.To identify prognostic factors of TC and provide real-world evidence,the first part of this study retrospectively reviewed the clinical data of TC patients in a single center,finding that complete resection of tumor and radiotherapy were independent protective factors.For patients with advanced disease,adjuvant radiotherapy and chemoradiation could be beneficial.In addition,we constructed two prognostic models,involving TNM system and Masaoka system respectively,to predict overall survival and progression-free survival of TC patient.Through comparing the calibration and discrimination of the two models,we found that the model involving TNM system is slightly superior to the one involving Masaoka system.Through involving different treatment modality,these models might help making clinical decisions.In recent years,the development of high-throughput sequencing technology and the application of bioinformatic analysis have provided new measures for cancer mechanism studying and diagnostic and therapeutic targets identifying.Finding effective diagnostic and therapeutic targets is the key area in TC research.The second part of the present study used weighted gene co-expression network analysis(WGCNA)on sequencing data acquired from public databases,identifying the gene modules that related to the stage of TC significantly.After survival and functional enrichment analysis,we finally screened 6 genes that related to the survival of TETs.These genes,CD3G,GRAP2,RASGRP1,ITK,LAT,and TTK,may affect the development of TC by regulating cell cycle process and T cell receptor signaling pathway,and may act as potential therapeutic targets.The third part of the present study identified 4 genes using WGCNA and differential expression analysis that have potential of differentiating TC from thymoma and normal tissues.These genes,GAL3ST3,NPTX1,PSMB11,and MSLN,may play a role in the diagnosis of TC. |
