自噬相关基因ATG2B、ATG4D、ATG9B在浸润性乳腺癌中的表达及临床意义

Expressions and Clinical Significance of Autophagy-related Genes ATG2B, ATG4D, ATG9B in Breast Carcinoma

中文关键词:  自噬相关基因 乳腺癌 表达

英文关键词:Autophagy-related genes Breast carcinoma Expression

中文摘要:

      目的 检测自噬相关基因ATG2B、ATG4D、ATG9B在乳腺癌细胞系及人乳腺癌组织中的表达，探讨3个基因可能的临床意义及对乳腺癌进展的影响。 方法 采用Cancer Browser筛查ATG2B、ATG4D、ATG9B 3个基因在乳腺癌中的表达情况；荧光定量RT-PCR检测4种乳腺癌细胞系（MCF-7、MDA-MB-231、MDA-MB-435S和ZR-75-30）以及83例乳腺癌组织中3个基因的表达量，进一步分别分析其表达与乳腺癌临床病理特征的关系。 结果 通过Cancer Browser筛查出乳腺癌中存在异常表达基因ATG2B、ATG4D、ATG9B（P=0.015，P=0.028，P=0.040）；4种细胞系均表达ATG2B、ATG4D、ATG9B,且ATG2B、ATG9B在4种乳腺癌细胞系中的表达均低于阳性对照中该基因的表达( P<0.001)，而ATG4D在乳腺癌细胞系中的表达高于阳性对照中的表达( P<0.001)；ATG2B、ATG4D、ATG9B基因在乳腺癌组织中的表达均低于在乳腺癌旁组织（P<0.001,P=0.031,P<0.001)。ATG2B表达与雌激素受体状态( r =0.949， P=0.015)相关；ATG4D表达与年龄( r=-0.449， P=0.005)相关；ATG9B表达与腋窝淋巴结转移 (r =0.339，P=0.043）和细胞角质蛋白5/6相关（ r=0.533， P=0.043)，而3个基因的表达与其他临床病理参数均无关（P>0.05）。 结论 ATG2B、ATG4D、ATG9B在乳腺癌中低表达，猜测是潜在的抑癌基因，且ATG2B、ATG4D、ATG9B均可能作为乳腺癌预后不良的新的分子标记物。

英文摘要:

      Objective To investigate the expressions and clinical significance of autophagy-related gene 2B （ATG2B），autophagy-related gene 4D （ATG4D） , autophagy-related gene 9B（ATG9B） in breast cancer cell lines and breast cancer. Methods Cancer Browser screening was applied to study the differential expressions ofATG2B, ATG4D, ATG9Bgenes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues. The relationships between the expressions of these genes and clinicopathological characteristics were further analyzed. Results Cancer Browser screening found abnormal expressions of ATG2B, ATG4D, ATG9Bin breast cancer （ P=0.015， P=0.028， P=0.040）. All four breast cancer cell lines expressed ATG2B, ATG4D, ATG9B,and the expression of ATG2B, ATG9B was significantly lower than positive control ( P<0.001), but ATG4D expression was higher than positive control ( P<0.001). The expressions of ATG2B, ATG4D, ATG9B in breast cancer were all lower than those in the adjacent normal tissues ( P<0.001, P=0.031, P<0.001). Furthermore, the expression of ATG2B was correlated with ER ( r =0.949， P=0.015), and the expression of ATG4D was related to age ( r =-0.449， P=0.005), the expression of ATG9B was correlated to lymph node metastasis and cytokeratin 5/6 status ( r =0.339， P=0.043; r =0.533， P=0.043). Conclusion ATG2B, ATG4D, ATG9Bgenes shows low expressions in breast cancer, which may become new molecular markers for the prognosis of breast cancer.