| Giant cell tumor(GCT)is a kind of primary bone tumor with strong invasiveness.Although it is benign in clinical morphology and imaging,it usually has malignant biological behavior,with less metastatic cases and few cases of self-healing tendencies.In addition,it is easy to delay treatment due to unclear judgment in clinical practice.Generally,solid tumors are usually surrounded by a fibrous tissue and have a clear boundary with the surrounding tissue.However,in cases of aggressive giant cell tumors,where the reactive crust is thin or has been destroyed,the tissue of giant cell tumor of bone can invade adjacent muscle or adipose tissue.In fact,the occurrence and development of tumors is a multi-factor and multi-step complex process.More and more studies have found that abnormal expression of genes and mutations plays an important role in tumorigenesis.However,in recent years,with the understanding of related oncogenes,tumor suppressor genes and their influencing factors in the process of tumorigenesis and development,molecular markers of tumorigenesis and the signaling pathways involved in the occurrence and development of tumors attract more and more people’s attention.This project conducts cell,tissue and genetic studies on the clinical factors,molecular markers and other directions of giant cell tumor of bone,so as to better guide the determination of surgical plans for giant cell tumor of bone,and provide a certain theoretical basis for the diversity and effectiveness of clinical treatment options.In this study,the clinicopathological factors of giant cell tumor of bone were analyzed,and the susceptibility genes of giant cell tumor of bone were investigated and verified in tissue samples,which were divided into the following three parts:Part Ⅰ: The retrospective clinical study was used to collect and follow up the cases in Tianjin Hospital in the past 15 years,and the indicators such as functional effect,oncology results,surgical resection and reconstruction were summarized to understand the diagnosis and treatment of giant cell tumor in Tianjin Hospital.Then,surgical elements of giant cell tumor of bone were analyzed according to the retrospective results and relevant evidence-based evidence,including surgical program,tumor resection,etc.,to unify the research treatment methods of giant cell tumor of bone in various sites.The first part of this project collected surgical cases from Tianjin Hospital from 2002 to 2017,and conducted follow-up,statistics,COX regression multi-factor analysis and other medical records analysis,and compared the effects of surgical methods,gender,age,pathogenesis and classification on postoperative recurrence and giant cell tumor.Part Ⅱ: Tissue and hematological specimens were used to screen for abnormal or susceptible genes,that is,whole exome sequencing was performed on tissue specimens and corresponding blood specimens.Meanwhile,through comprehensive genetic analysis,molecular typing of bone giant cell tumor was established to enrich the pathological features of bone giant cell tumor.The second part used whole exome sequencing to analyze the susceptibility genes and related pathways of giant cell tumor.Part Ⅲ: By collecting 149 cases of pathological wax blocks of giant cell tumor of Tianjin Hospital,tissue microarray was made to verify the markers related to tumor grading,tumor recurrence and metastasis found in the previous part.The correlation between the above candidate genes and the pathological grade of giant cell tumor was analyzed by techniques such as tissue microarray and immunohistochemistry.Results: The lowest recurrence rate was achieved in the tumor resection group(11.9%)compared with scratch in the lesion(45.5%)and extended curettage(21.6%)by comparing the recurrence rates of three surgical approaches,including scratch in the lesion,extended curettage and the tumor resection.However,the Enneking score after surgery is 28.97,which is significantly higher than the other two groups.Compared with the clinical features of recurrence and survival rate,there was no significant difference in the recurrence-free survival rate between the male and female patients with giant cell tumor of bone(P>0.05);the recurrence-free survival rate of patients aged <30 years was significantly lower than that of age >30 years(P<0.05).There was no significant difference in the recurrence-free survival rate among the patients with giant cell tumor of bone(P>0.05).There was no significant difference in the recurrence-free survival rate among patients with giant cell tumor of Campanacci grade I,II and III(P>0.05).The impact of soft tissue invasion and surgical methods on recurrence was significant(P<0.05).12 genes were selected as candidate genes of susceptibility genes of giant cell tumor of bone by whole exome sequencing.MMP-9,MMP-21 and MMP-29 belong to MMP(matrix metalloprotein)family;CD34,CD105 and CD68 belong to cadherin family,whose structure includes three parts: extracellular region,transmembrane region and cytoplasmic region;PTHLP;ANXA1,PRDX1,YWHAQ;MCC is related genes of "Sleeping Beauty" transposon;LRP5 belongs to WNT pathway related gene.Finally,three candidate genes,including AXNA1,YWHAQ and PRDX1,were found by tissue microarray.Results of tissue microarray showed that both AXNA1 and YWHAQ were related to the pathological grading of giant cell tumor of bone(P<0.05),but no correlation was found between PRDX1 and pathological grade(P>0.05).Conclusions: The recurrence rate of tumor resection is the lowest,but the surgical plans should be scientifically designed according to the actual grading of the cases and imaging analysis,because the impact of soft tissue invasion and surgical method on recurrence is significant.12 genes were selected as candidate genes for susceptibility genes of giant cell tumor of bone by whole exome sequencing.Results of tissue microarray showed that both AXNA1 and YWHAQ were related to the pathological grade of giant cell tumor of bone,but PRDX1 had no significant correlation with pathological grade. |
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