XIAP、Smac表达与乳腺癌新辅助化疗后腋窝阳性淋巴结病理完全缓解及预后的相关性

Correlation of XIAP and Smac expression with pathological complete response and prognosis of axillary positive lymph nodes after neoadjuvant chemotherapy for breast cancer

目的 探究抑制X染色体连锁的凋亡抑制蛋白(XIAP)、第二个线粒体衍生的半胱氨酸蛋白酶激活剂(Smac)表达与乳腺癌新辅助化疗(NACT)后腋窝淋巴结(ALN)阳性病理完全缓解(pCR)及预后的相关性。方法 选取2019年6月至2021年6月期间唐山市妇幼保健院收治的195例乳腺癌ALN阳性患者纳入乳腺癌组,所有患者均进行NACT,NACT前所有患者均进行活检穿刺取病灶组织。另同期选取195例经进行乳腺活检穿刺,且病理证实为良性乳腺结节的患者,纳入对照组。采用免疫组化法检测患者XIAP、Smac表达水平。根据乳腺癌患者NACT疗效分为pCR组及非pCR组,收集患者临床资料,采用单因素和多因素Logistic回归模型分析NACT后ALN阳性患者非pCR的影响因素,采用Kaplan Meier法分析不同XIAP、Smac表达情况患者的生存预后情况。结果 乳腺癌组病灶组织XIAP低表达占比低于对照组,Smac低表达高于对照组(P<0.05);195例患中72例患者NACT后pCR,pCR发生率为36.92%;非pCR组AJCCⅢ期、原发病灶直径>3.5 cm、ALN数量≥4个、ALN pN1~pN2期、XIAP高表达及Smac低表达占比均高于pCR组(P<0.05);Logistic回归分析模型结果显示,AJCCⅢ期、ALN数量≥4个、ALN pN1~pN2期、XIAP高表达及Smac低表达是乳腺癌患者NACT后ALN阳性非pCR的独立危险因素(P<0.05,OR>1);乳腺癌患者随访时间12~36个月,中位随访时间26个月,Kaplan Meier生存分析显示,XIAP低表达者3年累积生存率为94.9%,高于XIAP高表达者的90.4%(Log rank χ^(2)=4.931,P=0.026);Smac低表达者3年累积生存率为89.8%,低于Smac高表达的94.0%(Log rank χ^(2)=4.534,P=0.033)。结论 乳腺癌ALN阳性患者组织中XIAP异常高表达,Smac异常低表达,XIAP高表达及Smac低表达是乳腺癌患者NACT后ALN阳性非pCR的独立危险因素,XIAP低表达、Smac高表达患者生存率更高,预后更好。

Objective To investigate the correlation between the expression of X-linked apoptosis suppressor protein(XIAP)and the second mitochondria-derived cysteine protease activator(Smac)and pathologic complete response(pCR)of axillary lymph node(ALN)positive and prognosis of breast cancer after neoadjuvant chemotherapy(NACT).Methods A total of 195patients with ALN positive breast cancer admitted to our hospital from June 2019to June 2021 were included in the breast cancer group.All patients underwent NACT,and all patients underwent biopsy before NACT to obtain lesion tissue.In the same period,195patients with benign breast nodules confirmed by pathology were selected and included in the control group.The expression levels of XIAP and Smac were detected by immunohistochemistry.Breast cancer patients were divided into pCR group and non-PCR group according to NACT efficacy,and clinical data of patients were collected.Univariate and multivariate Logistic regression models were used to analyze the non-PCR influencing factors in ALN-positive patients after NACT.Kaplan Meier method was used to analyze the survival and prognosis of patients with different XIAP and Smac expressions.Results The low expression of XIAP in breast cancer group was lower than that in control group,and the low expression of Smac was higher than that in control group(P<0.05).Among the 195patients,72patients had post-NACT pCR,and the incidence of pCR was 36.92%.The proportion of AJCCⅢstage,primary lesion diameter>3.5cm,number of ALN≥4,ALN pN1~pN2 stage,high XIAP expression and low Smac expression in non-PCR group were higher than those in pCR group(P<0.05).Logistic regression analysis model showed that AJCC stageⅢ,ALN number≥4,ALN pN1~pN2stage,highXIAP expression and low Smac expression were independent non-PCR risk factors for positive ALN after NACT inbreast cancer patients(P<0.05,OR>1).Patients were followed up for 12to 36months,with a median follow-up timeof 26months.Kaplan Meier survival analysis showed that the 3-year cumulative survival rate of patients with low XIAPexpression was 94.9%,which was higher than that of patients with high XIAP expression(Log rankχ^(2)=4.931,P=0.026).The 3-year cumulative survival rate was 89.8%in patients with low Smac expression,which was lower than94.0%in patients with high Smac expression(Log rankχ^(2)=4.534,P=0.033).Conclusion XIAP expression is abnormally high and Smac expression is abnormally low in tissues of ALN-positive breast cancer patients.High XIAP expression and low Smac expression are independent non-PCR risk factors for ALN-positive breast cancer patients afterNACT.Patients with low XIAP expression and high Smac expression have higher survival rate and better prognosis.