Single-cell transcriptome reveals features of immune environment and mechanisms of immune escape in giant cell tumor of bone / 中华骨科杂志

Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.

Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application / 中华肿瘤杂志

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.

TBX2 gene mutation and the clinical significance of related proteins expression in ma-lignant peripheral nerve sheath tumor / 中国肿瘤临床

Objective:To detect genomic aberrations and investigate the expression and clinical significance of TBX2,CHK2, and p53 in malignant peripheral nerve sheath tumor (MPNST) tissues. Methods:We collected 63 cases of MPNST tissue samples, which were re-moved by resection and were confirmed by pathology, from January 1991 to December 2011 in Department of Bone and Sofer Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital. Twelve fresh tumor samples with qualified DNA quality were selected from the above 63 cases of tissue samples. Genome abnormalities of 12 MPNST tissues were detected by next-generation sequencing. The protein expression levels of TBX2, CHK2, and p53 in 63 MPNST tissue samples were assessed by immunohistochemistry staining. Results:One case of TBX2 gene mutation was observed out of the 12 MPNST tissue samples. In 63 MPNST tissue samples, the protein expression rates of TBX2, CHK2, and p53 were 60.3%(38/63), 47.6%(30/63), and 30.2%(19/63), respectively. TBX2 expression was sig-nificantly correlated with AJCC (American Joint Committee on Cancer, AJCC) stage, recurrence, and metastasis (P<0.05). TBX2 expres-sion was directly correlated with that of CHK2 (r=0.254, P=0.045), and CHK2 expression was directly correlated with that of p53 (r=0.343, P=0.006). In terms of the disease-free survival and overall survival time, patients with high expression levels of TBX2, CHK2, and p53 had significantly worse prognosis than patients with low expression levels of TBX2, CHK2, and p53(all P<0.05). TBX2, CHK2, and p53 were independent prognostic factors of MPNST. Conclusion:TBX2 and its associated proteins may play important roles in MPNST development and progression. Detecting TBX2 expression may provide the theoretical basis for estimating the prognosis of patients with MPNST.

Genetic aberrations of key signaling pathways in human osteosarcoma / 中华骨科杂志

Objective To performed microarray-based comparative genomic hybridization (aCGH) detection and carried out pathway analysis to gain a systemic view on the pathway alterations of the genetically altered genes in human osteosarcoma.Methods aCGH experiments were carried on 10 fresh osteosarcoma samples to obtain recurrent copy number change pattern,then the samples were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify the altered pathways in the osteosarcoma.To validate the aberrations of these key pathways,the alterations of VEGF pathway were selected to confirm by the methods of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) osteosarcoma archival tissues.Results The KEEG analysis of aCGH data identified 33 genetically altered pathways in osteosarcomas.Among them 20 pathways were identified genetic amplifications,such as VEGF and mTOR signaling pathways.Thirteen pathways were genetic deletions,such as Wnt and Hedgehog signaling pathways.The genetic aberrations of cell-cell-matrix pathway such as CAMs,Adherens junction and Tight junction pathways implied the genetically alterations of these pathways which are associated with the tumor invasion and metastasis.Validation the aberrations of VEGF pathway showed that VEGFA gene was significantly amplified.The positive protein expression of VEGFA had a significant association with microvessel density (MVD).Conclusion There are genetic aberrations which involved the component genes of VEGF,mTOR,CAMs,Adherens junction,Wnt,Hedgehog and other 26 signaling pathways.The alterations of these pathways which are significantly associated with tumor invasion,metastasis and progression suggest that the genetic aberrations of these key pathways might contribute to the tumorigenesis and progression in human osteosarcoma,and provide molecular genetic evidence for targeted therapy.

Mesenchymal to epithelial transition in malignant mesenchymal tu-mors / 中国肿瘤临床

Mesenchymal to epithelial transition (MET), whereby mesenchymal cells become more epithelial like in phenotype, was observed to occur during normal development and in cancers. Numerous investigations have been conducted on MET in carcino-mas. In addition, accumulating evidence also suggests the critical function of MET in sarcomas. Integrated analyses reveal that MET may be an important biological and clinical process in sarcomas, and transcription factors such as Slug may also perform central func-tions in epithelial differentiation in several sarcomas such as leiomyo-sarcoma and synovial sarcoma. Given the scarcity of investiga-tions and evidence, several important issues about MET, such as its molecular markers, signaling mechanisms, micro RNA regulations, and clinical significance, need to be clarified. In this article, we review several important questions about MET in sarcomas, including molecular markers, signaling mechanisms, regulation by miRNAs, and therapeutic implications.

Posterior laminectomy and vertebroplasty combined with radiofrequency ablation in spinal metastases from malignant tumors / 中国肿瘤临床

Objective:To investigate the safety and efficacy of laminectomy combined with vertebroplasty in spinal metastases from rapid-growth tumors. Methods:Clinical data of 23 patients with spinal metastases of lung cancer, who were admitted to the Cancer Hospital from July 2008 to May 2012, were retrospectively analyzed. Thirteen male and ten female patients, with an age range from 40 years to 65 years and a mean age of 51.5, were examined. All patients received posterior laminectomy to relieve spinal cord compression. Afterward, vertebroplasty combined with radiofrequency ablation was conducted, followed by the internal fixation of vertebrae (instrumental fixation). Operation time, blood loss, and bone cement leakage rate were analyzed. One month before and after the operation, pain measurement was conducted using visual analog scale (VAS) and neurologic deficit (spinal cord injury) by Frankel Grade. Functional impairment was classified by Karnofsky performance status (KPS) score. Quality of life was assessed by the European Organization for Research and Treatment questionnaire (EORTC QLQ-C30). Results:The mean operation time was 163±87.36 min. Blood boss was 430±130.35 mL. Bone cement leakage rate was 21.7%. One month before and after surgery, the VAS showed statistical significance (t=25.6, P<0.01). After surgery, 78.3%of all patients exhibited functionally satisfactory Frankel Grade D or E, compared with 43.5%of patients before the operation. KPS score (80 to 100) percentage was 69.6%after surgery compared with 34.8%before surgery. One month after the operation, remission of various degrees was seen in 10 of 18 patients who had sphincteric dysfunction before surgery (55.6%). The EORTC QLQ-C30 score was 85.39±8.99 before and 52.78±15.17 after operation. The quality of life improved significantly (t=11.6, P<0.01). Conclusion:Posterior laminectomy and vertebroplasty combined with radiofrequency ablation for spinal metastases from lung cancer is safe and effective. The treatment can improve pain, function, and life quality of patients with lung cancer spinal metastases.

Chondroblastoma in the long bone diaphysis: a report of two cases with literature review / 癌症

To investigate the clinical characteristics of chondroblastoma with an emphasis on lesions located in the long bone diaphysis, we reviewed the clinical data of 7 patients with histologically proven chondroblastoma treated in Tianjin Medical University Cancer Hospital and Fudan University Cancer Hospital between January 1995 and May 2009. There were two rare cases of chondroblastoma in the long bone diaphysis. One patient with a lesion in the tibial diaphysis underwent intralesional curettage and bone grafting, and the postoperative bone function was measured as excellent according to the Enneking scoring system. The patient was still alive upon follow-up at 60 months. The other patient with a lesion in the humeral diaphysis underwent resection, and the postoperative bone function was excellent at 48 months, at which there was no evidence of recurrence or metastasis. Thus, except for the distinctive site of the long bone diaphysis, which made diagnosis difficult, the patients' ages, symptoms, X-ray and CT images, treatment, and prognosis were in accordance with typical lesions in the epiphysis and metaphysis. The diagnosis of chondroblastoma in the long bone diaphysis significantly depends on histopathologic characteristics.

Related-factors analysis on early pathological fracture after curettage of benign tumors in femoral shaft / 中华骨科杂志

Objective To discuss the related factors of early pathological fracture after curettage of benign bone tumors in femoral shaft.Methods The clinical data of 47 patients with benign bone tumors in femoral shaft,treated by curettage with bone graft via the vastus lateralis approach from March 2004 to March 2011,were retrospectively analyzed.Thirteen patients of them presented with early pathological fracture after the curettage.In fracture group,there were 13 cases,11 males and 2 females,and the time from finishing curettage to fracture occurring ranged from 21 to 36 days.In non-fracture group,there were 34 cases,23 males and 11 females.The following data of fracture group and non-fracture group were compared and analyzed,such as specific value of absolute width of tumor and transverse diameter of bone shaft,specific value of defect width of bone window and sagittal diameter of bone shaft,defect length-width ratio of bone window,defect morphology of bone window,classification of bone tumor,violence of causing injury and compliance to medical advice.Results The average defect length-width ratio of bone window in fracture group was 3.72±3.58,in non-fracture group was 2.67±6.35.For classification of tumor,in fracture group 1 case was in incubation period,6 in active period,6 in invasion period; in non fracture group 21 cases were in incubation period,10 in active period,and 3 in invasion period.Four cases in fracture group had poor compliance to medical advice,and 9 in non-fracture group had good compliance.Between two groups,there were no statistical differences in specific value of absolute width of tumor and transverse diameter of bone shaft,specific value of defect width of bone window and sagittal diameter of bone shaft,and defect morphology of bone window.Conclusion When defect length-width ratio of bone window is larger than 4,the classification of tumor causes expanded incisal edge,and the cortical bone was damaged extensively,there are more possibilities for pathological fracture.

Radiofrequency ablation combined with subtotal corpectomy for spinal metastases / 中华骨科杂志

ObjectiveTo investigate the safety and efficacy of combined treatment with subtotal corpectomy and radiofrequency ablation(RFA) for spinal metastases. MethodsFrom April 2009 to March 2010, 29 patients with spinal metastases who received subtotal corpectomy were analyzed. Sixteen patients (7 men and 9 women) with an average of 57.8 years having received subtotal corpectomy alone were selected for comparison (the subtotal corpectomy group). Thirteen patients (7 men and 6 women) with an average of 58.3 years having received subtotal corpectomy combined with RFA were chosen as subjects of this study (the RFA combination group). There were no significant differences between the two groups with respect to the patient's age, gender, and Tomita type. Pain levels pre-and post-procedure were assessed by the visual analogue scale(VAS), and neurologic deficit were evaluated by the Frankel scale. ResultsThe VAS in RFA combination group were 8.88±0.36, 3.76±0.33, 3.35±0.38 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in subtotal corpectomy group were 8.96±0.39, 3.81 ±0.48, 3.41 ±0.42 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in both groups showed statistical significance at each time point, there was no statistically difference between the two groups. The operate time in RFA combination group and subtotal corpectomy group were(216.54±113.77) min and(302.50±80.44)min, respectively. The blood loss of the two groups were (1084.62±539.82)ml and (1625.00±724.34)ml, respectively. The recurrent rate of the two groups were 30.8％ and 75.0％, respectively. The RFA combination group were lower in operate time, blood loss and recurrent rates than subtotal corpectomy group. Conclusion Compared with the subtotal corpectomy, the RFA combination can reduce the blood loss, operation time, and the recurrent rates.