| ObjectiveKeloid(KD)is a kind of pathological scar,which is characterized by single or more protruding mass-like tissue on the surface of the skin,which grows continuously and gradually to the surrounding normal skin with exceeding the scope of the original lesion.Histopathology showed a large number of collagen fibers which were irregular,dense,thick and vitreous,with more type Ⅰ and type Ⅲ collagen at the edge,which may be related to local invasiveness.KD is easy to relapse after operation,with stronger proliferation,faster speed and larger range,so it is difficult to distinguish from benign or malignant skin tumors.The typical clinical and pathological features of KD suggest that it may be related to skin or mesenchymal tumors.Studies have confirmed that the similarities between KD and mesenchymal tumors can be found in the series of features from the expression of biomarkers to clinical manifestations.Fibrous histioncytoma(FH)and Dermatofibrosarcoma protuberana(DFSP)are common mesenchymal tumors with similar origin,including the global activation of Wnt β-catenin pathway in fibroid tumors and the increase of transforming growth factor β and collagen levels in DFSP.Differentiation of fibroblasts,myofibroblasts and histiocytes often occurs in the same tumor at the same time,and keloidal fibers can be observed.Keloidal fibers are protruding hard masses on the body surface,infiltrative growth,non-spontaneous regression,a certain recurrence rate,etc.,but the therapeutic effect is obviously different.Accurate preoperative diagnosis and correct and standardized treatment are very important for the prognosis.If necessary,immunohistochemistry and gene detection have important differential significance.The purpose of this study is to provide a basis for early clinical diagnosis by comparing and analyzing the clinical datas,pathological features and immunophenotyping of KD,FH and DFSP.In addition,this study used bioinformatics method to select the corresponding gene chip set from the Gene Expression Omnibus(GEO),the differential genes were screened out,and further analyzed their bioligical process,molecular function,cellular component and related pathways,so as to provide the basis for the pathogenesis and further study of the disease.MethodsPart one:a retrospective analysis of the data of pathologically diagnosed KD or FH or DFSP in the first affiliated Hospital of Zhengzhou University from January 2015 to January 2020.204 patients were followed up successfully and effectively,with a total of 215 lesions,including KD in 75 cases(80 lesions),FH in 70 cases(74 lesions)and DFSP in 59 cases(61 lesions).During the follow-up from 11 months to 4 years,the recurrence was recorded.The gender,age,etiology,concomitant symptoms,lesion size,lesion location,clinical signs,preliminary diagnosis,histopathology and recurrence of the three groups were statistically analyzed by SPSS26.0 software.The clinical and pathological features of KD,FH and DFSP were compared and analyzed.Part two:to select gene chip set from GEO public database with bioinformatics method,differential genes were screen out,and further analyzed their cellular component,molecular function,bioligical process and related pathways,and explored their similarities and differences in genetics.Results1 General datas:the age of DFSP group was higher than that of KD and FH(P<0.05).FH mostly occurred in the extremities(58.11%).The lesion area was smaller than that of KD and DFSP.There were many causes of KD(67.5%),most of which were accompanied by itching or tingling(67.5%).There was no significant difference between KD and DFSP in the location and size of lesions(P>0.05),and there was no difference in gender among the three diseases(P>0.05).2 Clinical signs:most of the FH were red(29.73%)or brown(28.38%),round(44.59%),with a clear boundary with the surrounding tissues(62.16%),while most of the KD and DFSP were red or skin color,irregular shape and unclear boundary with the surrounding tissues.There was no difference in the texture and activity of the lesions among the three groups(P>0.05).During the follow-up from 11 months to 4 years,the recurrence rate of KD was 47.5%,and FH was 6.76%,and DFSP was 26.23%.3 Pathological features:hirregular arrangement of thick collagen fibers could be seen in KD,with Vimentin(+),SMA focal expression,Ki-67<5%(+).In FH,short spindle cells proliferated to form short cross bundles,which were interwoven around collagen bundles,with SMA(+),Ki-67(1%-20%+),In DFSP,monomorphic spindle cells proliferated,arranged in storiform pattern,and infiltrated adipose tissue like honeycomb,with CD34 strongly and diffusely expressed,Ki-67(3%-60%+).4 The common genes of KD and DFSP were mainly involved in the cellular component of collagen-containing extracellular matrix.The related genes are:F3,OMD,TGM2,SEMA3B,SPON1.It mainly enriches the disorders of transcriptional misregulation in cancer and the related genes are CD14,HOXA11,IGFBP3 and MEIS1.5 KD unique gene was mainly involved in the cellular component and bioligical process,which was extracellular matrix component and embryonic organ development,and mainly enriched in Wnt signal pathway.DFSP unique genes were involved in the biological process of mesenchyme development and extracellular structure organization.Conclusions1 KD,FH and DFSP are similar in general datas and clinical signs,so it is difficult to make early differential diagnosis,especially between KD and DFSP.The histopathology has different characteristics.If necessary,the diagnosis can be confirmed by immunohistochemistry or gene detection.2 The cellular component of KD mainly includes collagen-containing extracellular matrix.DFSP participates in the development of mesenchyme development and enriches transcriptional misregulation in cancer.The differential diagnosis of diseases can be made by the characteristics of the unique genes.3 KD enriches in estranscriptional misregulation in cancer and Wnt signaling pathways,which provides basis for the study of pathogenesis.Through further using molecular biology techniques,we can find possible therapeutic targets and more ideas for KD treatment can be provided. |
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