CACNA1C基因表达水平对弥漫性大B细胞淋巴瘤利妥昔单抗耐药的预测价值

目的:探讨钙离子通道A1C（calcium voltage-gated channel subunit alpha1 C，CACNA1C）基因表达水平对弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）患者利妥昔单抗耐药的预测价值。方法:选取我院在2015年3月至2017年5月收治的DLBCL患者93例，均采用利妥昔单抗+CHOP方案化疗，随访2年，根据淋巴瘤化疗疗效评定标准，分为利妥昔单抗耐药组和敏感组；免疫组化法检测所有患者肿瘤组织的钙调蛋白CACNA1C基因、B淋巴细胞瘤-2（B-cell lymphoma-2，BCL-2）基因、PRDM1基因表达情况；绘制受试者工作曲线（receiver operating characteristic curve，ROC），分析CACNA1C基因、BCL-2基因、PRDM1基因水平在预测DLBCL利妥昔单抗耐药中的效能。结果:93例患者中共出现利妥昔单抗耐药病例26例，耐药率为27.96%；在一般资料方面耐药与敏感病例比较差异无统计学意义（P>0.05）；耐药组患者CACNA1C着色细胞比例（40.12±15.44)% vs (69.62±17.65）%低于敏感组，BCL-2着色细胞比例（66.31±15.92)% vs (47.43±14.66）%高于敏感组，PRDM1着色细胞比例（73.42±21.64)% vs (56.73±18.59）%高于敏感组，差异具有统计学意义（P<0.05）；ROC曲线显示，CACNA1C基因（AUC=0.848，95%CI=0.765~0.932）曲线下面积大于BCL-2基因（AUC=0.777，95%CI=0.673~0.881）和PRDM1基因（AUC=0.615，95%CI=0.486~0.744）；CACNA1C与BCL-2基因表达联合预测的曲线下面积（AUC=0.915，95%CI=0.854~0.976）显著高于三种基因表达水平单独预测，其中CACNA1C基因的最佳截点值为58.61%，BCL-2的最佳截点值为48.33%，此时联合预测在预测利妥昔单抗耐药的敏感性和特异性分别为80.77%和89.55%。结论:CACNA1C基因表达水平在预测DLBCL患者利妥昔单抗耐药方面具有较好的价值，其中CACNA1C与BCL-2联合预测利妥昔单抗耐药价值更高。

Predictive value of CACNA1C gene expression level in rituximab resistance to diffuse large B-cell lymphoma

Objective:To investigate the predictive value of calcium channel protein CACNA1C gene expression level for rituximab resistance in diffuse large B-cell lymphoma.Methods:93 patients with DLBCL admitted to our hospital from March 2015 to May 2017 were treated with R+CHOP regimen for 2 years.According to the criteria for lymphoma chemotherapy efficacy，they were divided into drug-resistant group and sensitive group.The calmodulin CACNA1C gene，B-cell lymphoma-2 (BCL-2) gene and PRDM1 gene expression were detected.The receiver operating characteristic curve (ROC) was mapped and the CACNA1C gene，BCL-2 gene，PRDM1 gene levels were analyzed in predicting the diagnostic efficacy of DLBCL rituximab resistance.Results:There were 26 cases of rituximab resistance in the 93 patients，and the drug resistance rate was 27.96%.There was no significant difference in the general data between the drug-resistant group and the sensitive group (P>0.05).The proportion of CACNA1C stained cells in the drug-resistant group (40.12±15.44)% vs (69.62±17.65)% was lower than that in the sensitive group，and the proportion of BCL-2 stained cells (66.31±15.92)% vs (47.43±14.66)% was higher than that of the sensitive group，and the ratio of PRDM1 stained cells (73.42±21.64)% vs (56.73±18.59)% was higher than the sensitive group.The difference was statistically significant (P<0.05).The ROC curve showed that the area under the CACNA1C gene (AUC=0.848，95%CI=0.765~0.932) was larger than the BCL-2 gene (AUC=0.777，95%CI=0.673~0.881) and the PRDM1 gene (AUC=0.615，95%CI=0.486~0.744).The area under the curve of CACNA1C combined with BCL-2 gene expression (AUC=0.915，95%CI=0.854~0.976) was significantly higher than the expression levels of the three genes alone.The best cutoff value of CACNA1C gene was 58.61%，and the best cutoff value of BCL-2 was 48.33%.At this time，the sensitivity and specificity of the combined diagnosis in predicting rituximab resistance were 80.77% and 89.55%，respectively.Conclusion:The expression level of CACNA1C gene has a good predictive value in evaluating rituximab resistance in patients with DLBCL.CACNA1C combined with BCL-2 can predict the higher value of rituximab resistance.