ANCCA Protein Expression is a Novel Independent Poor Prognostic Marker in Surgically Resected Lung Adenocarcinoma
ANCCA Protein Expression is a Novel Independent Poor Prognostic Marker in Surgically Resected Lung Adenocarcinoma
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DOI：
10.1245/s10434-013-3027-1
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发表时间：
2013-12-01
影响因子：
3.7
通讯作者：
Ji, Hongbin
中科院分区：
文献类型：
--
作者：
Zhang, Yang;Sun, Yihua;Ji, Hongbin
背景。研究发现 AAA+ 核共调节器癌症相关 (ANCCA) 在各种癌症类型中过度表达，并且可能在常见和基本的细胞过程中发挥作用。最近的一项研究表明，ANCCA 可能是一个驱动因素，其表达解释了肺腺癌中差异表达的增殖相关基因的行为。然而，肺腺癌中 ANCCA 的蛋白表达及其与临床病理参数和常见报告的驱动突变的关联仍未得到探索。方法。通过免疫组织化学方法评估 143 例手术切除的肺腺癌中的 ANCCA 表达，并与临床病理学和分子变量相关，包括腺癌组织学亚型、肿瘤、淋巴结、转移状态、无复发生存期、总生存期、EGFR 突变、KRAS 突变、HER2 突变和 ALK 融合。结果。 ANCCA 阳性表达与男性、吸烟者、低分化肿瘤、非鳞屑为主的亚型、更晚期的 T 分期、淋巴结转移和晚期疾病阶段显着相关。 Cox 多变量分析显示，ANCCA 阳性表达是较差无复发生存率的独立预测因子[风险比 (HR) 1.736，95% 置信区间 (CI) 1.075-2.804； P = .024）和总生存率（HR 7.758，95% CI 2.955-20.370；P < .001）。将 ANCCA 蛋白表达添加到使用病理分期的预后模型中，显着提高了预后准确性；一致性指数从0.692增加到0.788，赤池信息标准从354.20下降到336.11。结论。我们已经确定 ANCCA 蛋白表达是肺腺癌中一种新的独立的不良预后指标。有必要进行前瞻性研究，以结合当前的分期系统来验证其潜在的预后价值。
Background. AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored.Methods. ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions.Results. Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11.Conclusions. We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.