Yang Jing, Wu Ning-Ni, Huang De-Jia, Luo Yao-Chang, Huang Jun-Zhen, He Hai-Yuan, Lu Hai-Lin, Song Wen-Ling
1 Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
2 Department of Medical Oncology, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Tumour Biol. 2017 Jul;39(7):1010428317713492. doi: 10.1177/1010428317713492.
Although the oncogenic role of PPFIA1 (liprin-α1) in breast cancer has been reported, whether its dysregulation is associated with metastasis risk or survival outcomes in breast cancer patients is not clear. Our primary data showed that PPFIA1 expression was significantly higher in liver metastatic breast tumors than in the primary tumors. Then, we tried to pool previous annotated genomic data to assess the prognostic value of PPFIA1 in distant metastasis-free survival, the risk of metastatic relapse, and metastatic relapse-free survival in breast cancer patients by data mining in two large databases, Kaplan-Meier plotter and bc-GenExMiner 4.0. Results from Kaplan-Meier plotter showed that although high PPFIA1 expression was generally associated with decreased distant metastasis-free survival in estrogen receptor+ patients, subgroup analysis only confirmed significant association in estrogen receptor+/N- (nodal negative) group (median survival, high PPFIA1 group vs low PPFIA1 cohort: 191.21 vs 236.22 months; hazard ratio: 2.23, 95% confidence interval: 1.42-3.5, p < 0.001), but not in estrogen receptor+/N+ (nodal positive) group (hazard ratio: 1.63, 95% confidence interval: 0.88-3.03, p = 0.12). In estrogen receptor- patients, there was no association between PPFIA1 expression and distant metastasis-free survival, no matter in Nm (nodal status mixed), N-, or N+ subgroups. In bc-GenExMiner 4.0, Nottingham Prognostic Index- and Adjuvant! Online-adjusted analysis validated the independent prognostic value of PPFIA1 in metastatic risks in estrogen receptor+/N- patients. Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N- breast cancer, but not in estrogen receptor+/N+ or estrogen receptor- patients.
尽管已有报道PPFIA1（liprin-α1）在乳腺癌中具有致癌作用，但其失调是否与乳腺癌患者的转移风险或生存结果相关尚不清楚。我们的原始数据显示，肝转移性乳腺肿瘤中PPFIA1的表达明显高于原发性肿瘤。然后，我们试图汇总先前注释的基因组数据，通过在两个大型数据库Kaplan-Meier plotter和bc-GenExMiner 4.0中进行数据挖掘，评估PPFIA1在乳腺癌患者无远处转移生存期、转移复发风险和无转移复发生存期中的预后价值。Kaplan-Meier plotter的结果显示，尽管PPFIA1高表达通常与雌激素受体阳性患者的无远处转移生存期缩短相关，但亚组分析仅在雌激素受体阳性/N-（无淋巴结转移）组中证实了显著相关性（中位生存期，PPFIA1高表达组与低表达组：191.21对236.22个月；风险比：2.23，95%置信区间：1.42 - 3.5，p < 0.001），而在雌激素受体阳性/N+（有淋巴结转移）组中未发现相关性（风险比：1.63，95%置信区间：0.88 - 3.03，p = 0.12）。在雌激素受体阴性患者中，无论在Nm（淋巴结状态混合）、N-或N+亚组中，PPFIA1表达与无远处转移生存期均无关联。在bc-GenExMiner 4.0中，诺丁汉预后指数和辅助!在线调整分析验证了PPFIA1在雌激素受体阳性/N-患者转移风险中的独立预后价值。基于这些发现，我们推断PPFIA1高表达可能是雌激素受体阳性/N-乳腺癌患者转移复发风险增加的独立预后指标，但在雌激素受体阳性/N+或雌激素受体阴性患者中并非如此。
