| Background and Objectives:Dermatofibrosarcoma Protuberans(DFSP)was a rare.low-grade soft tissue sarcoma with a high recurrence rate and misdiagnosis rate,and rarely metastases.Sometimes DFSP can have fibrosarcoma-like changes,forming fibrosarcomatous DFSP(FS-DFSP).FS-DFSP was very easy to metastasize,and the prognosis wasrelatively poor.At present,the clinical reports of this disease are still rare in China.The purpose of this study was to describe the clinical and histopathological features of DFSP,the therapeutic effect,and to analyze the factors of recurrence and metastasis.Methods:The clinical data of DFSP patients treated in our hospital from January 1999 to July 2018 were analyzed through retrospective research methods.Further descriptive research on the tumor's onset location,age of onset and pathology and other clinical features,while analyzing the prognosis of patients,the endpoint of the study was the incidence of major disease-related clinical events.Results:This study collected case data of 254 patients,including 139 males and 115 females.The average age of DFSP diagnosis was 38.4±12.3 years(range:12-69 years),of which 188 cases(74.0%)were between 20-50 years old,19 cases(7.5%)were ?20 years old,and 47 cases(18.5%)age>50 years old.Tumors mainly occurred in the trunk,followed by upper and lower limbs,with 132 cases(52.0%),55 cases(21.7%)and 48 cases(18.9%)respectively.There were 248 cases of pathological type of classic DFSP(C-DFSP),6 cases of rare FS-DFSP.The pathology consultation in our hospital found that 49 patients had positive margins after local resection in the outer hospital,and 79 patients were confirmed to have residual tumors by pathology after surgery in our hospital.A total of 211 patients'follow-up data were available for analysis,with an average follow-up time of 38(1-196)months.The 5-year recurrence-free survival rate after wide-local excision(WLE)was 97.1%.Compared with patients treated with local resection,the local recurrence rate of patients treated with WLE was significantly lower(2.9%VS 37.7%;p<0.001).The distant metastasis rate of FS-DFSP(66.7%[n=4]VS 2.0%[n=4];p<0.001)and mortality(50.0%[n=3]VS 1.5%[n=3];p<0.001)was significantly higher than C-DFSP.A total of 8 patients in this group had distant metastases.The most common site of metastasis was the lung.The overall distant metastasis rate was 3.8%(8/211);the 1-year survival rate of patients with distant metastases was 87.5%(6/8),the 3-year survival rate was 25%(2/8).There was no significant difference in improving the recurrence free survival rate after WLE(p=0.042).Multivariate analysis showed that metastasis was an independent prognostic factor(p=0.042).Univariate analysis showed that the main factors of local recurrence were related to pathological types(?2=6.443,p=0.011);FS-DFSP was easier to transfer than C-DFSP(?2=19.522,p<0.001).Conclusion:DFSP was a low grade soft tissue tumor with rare metastasis.WLE was an effective method to reduce the recurrence of DFSP.The metastasis rate of FS-DFSP was significantly higher than that of C-DFSP,and the prognosis was poor.The local recurrence and metastasis after WLE were mainly related to the pathological type,adjuvant radiotherapy cannot improve the recurrence-free survival rate of tumors.Background and Objectives:Dermatofibrosarcoma protuberans(DFSP)was a very rare,locally aggressive cutaneous soft tissue sarcoma,with an incidence rate of about 1/100,0000.Although DFSP had certain characteristics in histological morphology and molecular genetics,due to the wide variety of histological classifications,immunomics still lacks specific molecules.and it was easy to be confused with other tumors such as fibrosarcoma and fibroids in clinical diagnosis.At present,most articles reported that the pathogenesis of DFSP was related to the fusion gene of PDGFB and COL1A1,but few studies explored the pathogenesis of DFSP from the perspective of differential proteomics.The purpose of this study was to analyze the proteomic differences between tumors and normal tissues adjacent to the recurrence of DFSP to find differential proteins that can cause recurrence of DFSP.and to provide more research evidence for the treatment of DFSP,especially the application of targeted drugs..Methods:Quantitative proteomics tandem mass tag(TMT)labeling technology was used for proteomic detection of tumor tissues and corresponding adjacent tissues of 3 patients with relapsed DFSP;and perform bioinformatics analysis of differential proteins,included screening of differentially expressed proteins.it also included hierarchical clustering analysis.In addition.it included KEGG Pathway Analysis.There were GO annotation enrichment Analysis and difference PPI network analysis of expressed protein,also included.GEPIA(Gene Expression Profiling Interactive Analysis)database was used to analyze whether the differential gene is related to PDGFB and COL1A1.Results:In this study,a total of 377 differential proteins were screened,including 246 up-regulated proteins and 131 down-regulated proteins.Through GO database analysis,it was found that differential proteins were involved in 801 biological process(BP)terms,1 12 molecular function(MF)terms,and 174 cellular component(CC)terms.In BP terms,differential proteins played a significant role in the processing of mRNA,splicing of RNA,and the metabolic process of organic compounds.In MF terms,differential proteins played a significant role in RNA binding,nucleic acid binding,organic compound binding,and protein binding.In CC terms,it mainly plays a significant role in the formation of organelles.KEGG analysis showed that it were involved in 18 signaling pathways,and the number of differentially proteins mapped to the spliceosome pathway was the largest.The top 10 genes were POLR2A,NCBP1,SF3B1,SNRPE,SNRPD1,SRSF1,SF3B3,PRPF31,POLR21,H-NRNPU Among them,POLR2A interacted with 39 genes/proteins(p=0.04073).The top 10 differentially expressed genes with the highest connectivity were verified by GEPIA database,among which POLR2A,SNRPE,SNRPD1,SF3B3,POLR21 and SF3B1were associated with COL1A1/PDGFB.Conclusion:TMT quantitative proteomics can screen the differential proteins between DFSP tumor and normal tissues.Differential proteins were involved in a variety of metabolic pathways in the occurrence and development of DFSP,and POLR2A may play a central role in the pathogenesis of DFSP. |
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