骨髓增生异常综合征危险分层与中医证候及其分子遗传学特点的关系分析

目的分析骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者的危险分层与中医证候的关系,初步探究MDS中医证候与分子遗传学特点的关系。方法综合MDS国际预后积分系统(IPSS、IPSS-R和IPSS-R-M)将72例MDS患者分为相对低危组和相对高危组,检测患者外周血、肝肾功、骨髓细胞形态学、突变基因等指标,收集中医四诊进行辨证并计算证候积分,制定并填写《病例报告表》,整理数据,分析MDS危险分层和中医证候分型、证候积分、基因突变的关系。结果中医辨证为气血两虚证的患者相对低危组(67.5%)多于相对高危组(25%)(P<0.05),辨证为瘀血内阻证的患者相对高危组(56.25%)多于相对低危组(15%)(P<0.05),差异有统计学意义;脾肾不足证相对低危组(17.5%)与相对高危组(18.75%)比较(P>0.05),差异无统计学意义。相对低危组与相对高危组均为气血两虚证证候积分最低,脾肾不足证证候积分稍高,瘀血内阻证证候积分最高。相对低危组的3个证型证候积分相比较,差异有统计学意义(P<0.05),两两比较,脾肾不足证与气血两虚证、气血两虚证与瘀血内阻证证候积分差异有统计学意义(P<0.05),脾肾不足证与瘀血内阻证证候积分差异无统计学意义(P>0.05);相对高危组的3个证型证候积分比较,差异有统计学意义(P<0.05),两两比较,气血两虚证与瘀血内阻证积分差异有统计学意义(P<0.05),脾肾不足证与气血两虚证、脾肾不足证与瘀血内阻证积分差异均无统计学意义(P>0.05)。就3个证型而言,无论哪种证型的证候积分,均是相对低危组较相对高危组低,P<0.05,差异有统计学意义。相对高危组基因突变率高于相对低危组(P<0.05)。3个中医证型中,脾肾不足证所检出最多的基因为TET2(3例,30%),气血两虚证为SF3B1(8例,57.14%),瘀血内阻证为TET2(9例,45%)。在各个常见突变基因中,SF3B1检出率最高的证型是气血两虚证(8例,57.14%),且3个证型的检出率相比较差异有统计学意义(P<0.05),SRSF2检出率最高的证型是瘀血内阻证(7例,35%),3个证型检出率比较差异有统计学意义(P<0.05),其余常见突变基因在3个证型中的检出率均无统计学差异(P>0.05)。结论MDS危险分层与中医证候分型、中医证候积分、基因突变之间存在着一定的规律性。

Analysis of Relationship Between Risk Stratification and TCM Syndromes in Patients with Myelodysplastic Syndrome and Its Molecular Genetic Characteristics

Objective To analyze the relationship between risk stratification and TCM syndromes of patients with myelodysplastic syndrome(MDS),and preliminarily explore the relationship between TCM syndromes and molecular genetic characteristics under different risk stratification of MDS.Method According to the comprehensive prognosis of MDS international integration system(IPSS,IPSS-R and IPSS-R-M),72 patients were divided into relatively low risk and relatively high risk groups.We detected peripheral blood,liver and kidney function,indexes of bone marrow cell morphology,mutations.After collecting four diagnosis in traditional Chinese medicine syndrome differentiation and syndrome integral calculation,filled out the case report form,sorted the data and analyzed the MDS risk stratification and classification of syndromes and syndrome integral,and the relationship between genetic mutations.Results The patients with Qi and blood deficiency syndrome(67.5%)in the low risk group were more than those(25%)of the high-risk group(P<0.05),and the patients with internal blood stasis syndrome(56.25%)of the high-risk group were more than those(15%)of the low-risk group(P<0.05),and the difference was statistically significant(P<0.05).The patients with deficiency of spleen and kidney(17.5%)of the low-risk group and those(18.75%)of the high-risk group were not statistically significant(P<0.05).The scores of Qi and blood deficiency syndrome were the lowest in both groups.The scores of spleen and kidney insufficiency syndrome were slightly higher,and the scores of internal blood stasis syndrome were the highest.The scores of the three syndrome types in the low-risk group were statistically significant(P<0.05).The spleen and kidney deficiency syndrome and syndrome of Qi and blood deficiency,syndrome of Qi and blood deficiency and syndrome of internal blood stasis were statistically significant(P<0.05),while the scores of spleen and kidney deficiency syndrome and syndrome of internal blood stasis were not statistically significant(P>0.05).The scores of the three syndrome types in the high-risk group showed statistically significant difference(P<0.05).The spleen and kidney deficiency syndrome showed statistically significant difference(P<0.05),while the scores of spleen and kidney deficiency syndrome showed no statistically significant difference(P>0.05).In terms of the three syndromes,the syndrome scores of each syndrome type were lower in the relatively low-risk group than those in the relatively high-risk group and the difference was statistically significant(P<0.05).The mutation rate of the high-risk group was higher than that of the low-risk group(P<0.05).Among the three TCM syndromes,TET2 was the most detected gene in spleen and kidney deficiency syndrome(3 cases,30%).SF3 B1 was the most detected gene in Qi and blood deficiency syndrome(8 cases,57.14%),and TET2 was the most detected gene in internal blood stasis syndrome(9 cases,45%).SF3 B1 detection rate was the highest in Qi and blood deficiency syndrome(8 cases,57.14%),and three syndrome types were statistically significant(P<0.05).The highest detected rate of SRSF2 was internal blood stasis syndrome(7 cases,35%),and the difference was statistically significant(P<0.05).The the detection rate of the rest common mutations in the three syndrome types had no statistical difference(P>0.05).Conclusion There is a certain regularity between MDS risk stratification and TCM syndrome classification,TCM syndrome integral and gene mutation.