高表达DNAJA1促进乳腺癌细胞增殖及侵袭且与患者的不良预后及化疗抵抗密切相关

目的:分析DNAJ热休克蛋白40家族成员A1［DNAJ heat shock protein 40 family（Hsp40) member A1，DNAJA1］在人乳腺癌组织中的表达及其与患者临床病理特征的关系，探讨DNAJA1对乳腺癌细胞增殖及侵袭的影响，揭示其与乳腺癌患者预后及化疗抵抗的关系。方法:免疫组织化学检测169例乳腺癌患者配对石蜡组织及120例接受新辅助化疗前穿刺活检石蜡组织中DNAJA1的表达情况。CCK-8、平板克隆、Transwell侵袭及细胞划痕实验检测DNAJA1对乳腺癌细胞增殖和侵袭的影响。结果:DNAJA1在原发灶及转移灶的乳腺癌组织中的表达明显高于癌旁组织（P＜0.001,P＜0.001）。临床病理分析发现，DNAJA1的高表达与分子分型、p53的突变和肿瘤复发密切相关。DNAJA1高表达还与患者的较短生存时间相关（P=0.023）。另外，DNAJA1在接受新辅助化疗的Miller-Payne（MP) 5级组患者的癌组织中表达明显低于其他组（P=0.000 4）。体外实验证实，敲低DNAJA1能明显抑制乳腺癌细胞的增殖和侵袭。结论:DNAJA1能促进乳腺癌细胞的增殖和侵袭，且DNAJA1在乳腺癌组织中高表达与患者不良预后及化疗抵抗相关，可作为预测患者预后及新辅助化疗效果的一个新靶点。

The high expression of DNAJA1 promotes the proliferation and invasion of breast cancer cells and is closely related to poor prognosis and chemotherapy resistance

Objective:To analyze the expression and clinicopathological correlations of DNAJ heat shock protein 40 family（Hsp40) member A1（DNAJA1),investigate the effect of DNAJA1 on proliferation and invasion of breast cancer cells and reveal its relationship with prognosis and chemoresistance in breast cancer patients.Methods:The expression of DNAJA1 in paired paraffin tissue of 169 breast cancer patients and paraffin tissue biopsy performed in 120 patients before neoadjuvant chemotherapy was detected by immunohistochemistry.CCK-8,plate colony,Transwell invasion and cell wound scratch assays were performed to evaluate the effect of DNAJA1 on the proliferation and invasion of breast cancer cells.Results:The expression of DNAJA1 in primary and metastatic breast cancer tissues was significantly higher than that paracacerous tissues（P＜0.001,P＜0.001).Clinicopathological analysis showed that the high expression of DNAJA1 was closely related to molecular typing,p53 mutation and tumor recurrence.High expression of DNAJA1 was also associated with shorter survival time(P=0.023).In addition,the expression of DNAJA1 in Miller-Payne（MP) grade 5 patients receiving neoadjuvant chemotherapy was significantly lower than that in other groups（P=0.000 4).Depletion of DNAJA1 obviously suppressed the proliferation and invasion abilities of breast cancer cells.Conclusion:DNAJA1 promotes the proliferation and invasion of breast cancer cells and its high expression of DNAJA1 in breast cancer is associated with poor prognosis and chemotherapy resistance.It can be used as a new target for predicting prognosis and efficacy neoadjuvant therapy of breast cancer patients.