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.

Survival analysis of 121 patients with spinal metastases accepted spinal surgery / 中华骨科杂志

Objective To investigate the safety and efficacy of surgery in 121 patients with spinal metastases.Methotds A retrospective analysis of clinical data from April 2009 to March 2013 was performed in 121 patients with spinal metastases.From 37 to 65 years,69 males and 42 females with mean age of 55.6 years.Primary tumor origin:Lung 35(28.9％),Breast 26(21.4％),Renal 17 (14.0％),Prostate 20 (16.5％),Thyroid 14 (11.6％),Liver 2 (1.7％),Colon 1 (0.8％),other 6 (5.0％).All patients received surgery.Follow-up and survival time were analyzed.In preoperation and postoperative 3 month,pain levels were assessed by visual analogue scale (VAS),neurologic deficit was evaluated by Frankel Grade and functional impairment was classified by Karnofsky Score.The quality of the life was assessed by EORTC QLQ-C30 questionnaire.Survival analysis was evaluated by Kaplan-meier.Results The period of follow-up ranged from 5 to 35 months with the average of 15.9 months.The mean survival was 14.5 months.1-year survival was 53.5％.2-year survival was 36.5％.In patients with lung cancer,the mean survival was 8.5months.1-year survival was 14.3％.2-year survival was 11.4％.In patients with breast cancer,the mean survival was 31 months.1-year survival was 57.7％.2-year survival was 46.2％.In preoperation and postoperative 3 month,the VAS showed statistical significance (t=21.6,P＜0.01) ;Post-operatively,80.3％ of all patients had functionally useful Frankel Grade D or E compared with 43.5％ pre-operatively.KPS score (80-100) percentage was 75.6％ postoperatively compared with 33.4％ preoperatively.In 1month postoperatively,35 of 75 patients who were sphincteric dysfunction preoperatively were improved.The EORTC QLQ-C30score was 83.39±7.23 in preoperation and 51.34±14.27 in postoperaion.The quality of life was impoved significantly (t=12.6,P＜0.01).Conclusion Surgical treatment was effective in improving quality of life by providing better pain control,enabling patients to regain or maintain mobility,and offering improved sphincter control.In all patients,the number of patents with spinal metastases from breast and lung cancer is higher.Compared with spinal metastases from breast cancer,the proportion of lung cancer origin received surgery is higher.

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.

Clinical analysis of twenty-eight patients with alveolar soft part sarcoma / 中国医师进修杂志

Objective To study the clinical features of alveolar soft part sarcoma (ASPS) and assess its prognostic factors.Methods The clinical data of 28 ASPS patients from January 2006 to January 2009 were analyzed retropectively,and were followed up to get their prognosis.The survival analysis and risk factors were analyzed and compared.Results Two cases with soft tissue primary ASPS got recurrence after the first resection,the recurrence rate was 8.0％ (2/25).After re-resection,no postoperative recurrence occurred.Three cases with bone primary ASPS did not have postoperative local tumor recurrence,but 2 cases appeared tumor progression and got pulmonary metastasis.All the patients had poor overall prognosis,11 cases survived without tumor,8 cases survived with tumor,9 cases died.The median survival time was 38.5 months,5-year survival rate was 46.4％ (13/28),5-yeax survival rate of male patients was 50.0％ (5/10),female patients was 44.4％(8/18),5-year survival rate between male and female patients had no statistical significance (P =0.260).The 5-year survival rate of patients without distant metastasis was 81.8％ (9/11),while the rate of patients with distant metastasis (pulmonary,brain or bone metastasis) was only 23.5％(4/17),and the rates had significant difference (P =0.036).Age,gender had no significant relation with the prognosis,while tumor size,location and distant metastasis were the important factors affecting the prognosis.Conclusions ASPS commonly occurs in young persons.The hips and thighs are the most common sites ofsofte tissue primary ASPS.Prognosis has relation with distant metastasis,tumor size and part or thorough resection.The risk of recurrency and metastasis can be decreased through assessing disease condition as soon as possible,developing a reasonable treatment plan and wide resection of the primary tumor.

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.