■探讨转化生长因子β(TGF-β)和肿瘤细胞坏死率(TCNR)在骨肉瘤中表达的临床意义及其化疗耐药对骨肉瘤的影响。收集
■2014年1月至2019年1月昆明医科大学第三附属医院新辅助化疗骨肉瘤患者94例。在化疗前收集测试TGF-β的样本,测定化疗前后病理标本的肿瘤细胞坏死率。其他分析的协变量包括12个预后因素,这些因素可能与先前研究中的化疗耐药有关:年龄,BMI,初始诊断时间(从症状发作到首次就医的时间),KPS评分,初始肿瘤大小,淋巴细胞/白细胞率(LWR),中性粒细胞/淋巴细胞率(NLR),白蛋白,天冬氨酸转氨酶(AST),低密度脂蛋白(LDL),血尿素氮(BUN),碱性磷酸酶(ALP),终点包括无进展生存期(PFS)和总生存期(OS),根据RECIST指南(1.1版),实体瘤的反应评估标准。
■1.共检测94例病理标本中TGF-β的表达,TGF-β高表达45例(47.9%),TGF-β低表达49例(52.1%);2.BMI,LDL,ALP,TGF-β高表达组NLR较TGF-β低表达组显著升高;TGF-β高表达组的KPS较TGF-β低表达组显著降低,均P<0.05;3.化疗效果与细胞阳性率(P<0.01r=0.337)和TGF-β总分(P<0.0001r=0.635)呈正相关。化疗效果与染色程度评分无相关性(P>0.05);TGF-β高表达组与TGF-β低表达组化疗后与基线比较差异有统计学意义(P=0.045);4.TGF-β高表达组的中位OS为61.4个月,TGF-β低表达组的中位OS68.1个月,一年生存率,两组比较差异有统计学意义(P=0.045);TGF-β高表达组的中位PFS为44.8个月,TGF-β低表达组的中位PFS为56.2个月,两组比较差异无统计学意义(P>0.05);5.共92例化疗后检查TCNR,62例TCNR≤90%(67.4%),30例TCNR>90%(32.6%);6.初始诊断时间,KPS,与TCNR≤90%组相比,TCNR>90%组显著增加;初始肿瘤大小,BUN,TCNR>90%组ALP明显低于TCNR≤90%组,所有P<0.05;7.TCNR与化疗后相对于基线的变化呈负相关(P<0.001r=-0.411);TCNR>90%组和TCNR≤90%组化疗后相对于基线的变化无统计学意义(P>0.05);8.TCNR>90%组的中位OS为67.8个月,TCNR≤90%组的中位OS为61.7个月,两组间差异有统计学意义(P=0.040);TCNR>90%组中位PFS57.4个月,TCNR≤90%组的中位PFS为40.5个月,两组间差异有统计学意义(P=0.036);9.TGF-β总分与TCNR呈负相关(P<0.001r=-0.571)。
■这项研究的结果表明,TGF-β的高表达,TCNR的低表达,骨肉瘤患者更容易诱导化疗耐药,导致预后不良。
UNASSIGNED: The clinical significance of transforming growth factor β (TGF-β) and tumor cell necrosis rate (TCNR) in the expression of osteosarcoma and its effects of chemotherapy resistance on osteosarcoma were explored.
UNASSIGNED: 94 cases of neoadjuvant chemotherapy osteosarcoma patients at the Third Affiliated Hospital of Kunming Medical University between January 2014 and January 2019 were collected. Samples tested for TGF-β were collected before chemotherapy, the tumor cell necrosis rate of pathological samples before and after chemotherapy was determined. Others analyzed covariates included 12 prognostic factors that may be associated with chemotherapy resistance in previous studies: age, BMI, initial diagnosis time (The time from symptom onset to first medical attention), KPS score, initial tumor size, lymphocytes/leukocytes rate (LWR), neutrophils/lymphocytes rate (NLR), albumin, aspartate transaminase (AST), low density lipoprotein (LDL), blood urea nitrogen (BUN), alkaline phosphatase (ALP), the endpoints included progression-free survival (PFS) and overall survival (OS), response evaluation criteria in solid tumours by RECIST guideline (version 1.1).
UNASSIGNED: 1. A total of 94 cases were examined for expression of TGF-β in pathological specimens, 45 cases were TGF-β high expression (47.9%) and 49 cases were TGF-β low expression (52.1%); 2. The BMI, LDL, ALP, NLR in TGF-β high expression group was significantly increased compared to TGF-β low expression group; the Initial diagnosis time, KPS in TGF-β high expression group was significantly decreased compared to TGF-β low expression group, all P < 0.05; 3. Effect of chemotherapy was positively with positive cell rate (P < 0.01 r = 0.337) and TGF-β total score (P < 0.0001 r = 0.635), while effect of chemotherapy was no correlation with degree of dyeing score (P > 0.05); there was significant difference in change from baseline after chemotherapy between TGF-β high expression group and TGF-β low expression group (P = 0.045); 4. Median OS 61.4 months in the TGF-β high expression group, median OS 68.1 months in the TGF-β low expression group, one-year survival rate, there was statistically significant difference in two groups (P = 0.045); median PFS 44.8 months in the TGF-β high expression group, median PFS 56.2 months in the TGF-β low expression group, There was no statistically significant difference in two groups (P > 0.05); 5. A total of 92 cases were examined for TCNR after chemotherapy, 62 were TCNR ≤ 90% (67.4%), 30 were TCNR > 90% (32.6%); 6. the Initial diagnosis time, KPS, in TCNR > 90% group was significantly increased compared to TCNR ≤ 90% group; the initial tumor size, BUN, ALP in TCNR > 90% group was significantly decreased compared to TCNR ≤ 90% group, all P < 0.05; 7. TCNR was negatively correlated with the change from baseline after chemotherapy (P < 0.001 r = -0.411); there was no statistically significant difference between TCNR > 90% group and TCNR ≤ 90% group in change from baseline after chemotherapy (P > 0.05); 8. Median OS 67.8 months in the TCNR > 90% group, median OS 61.7 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.040); median PFS 57.4 months in the TCNR > 90% group, median PFS 40.5 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.036); 9. TGF-β total score was negatively correlated with TCNR (P < 0.001 r = -0.571).
UNASSIGNED: The results of this study suggested that the higher expression of TGF-β, the lower expression of TCNR, which more likely to induce chemotherapy resistance among patients with osteosarcoma and lead to poor prognosis.