Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy
Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy
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DOI：
10.1177/1535370216632623
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发表时间：
2016-06-01
影响因子：
3.2
通讯作者：
Capelozzi, Vera
中科院分区：
文献类型：
--
作者：
Antonangelo, Leila;Tuma, Taila;Capelozzi, Vera
DNA结合抑制因子/分化抑制因子（Id）蛋白家族已被证明与癌症发生有关。然而，Id在肺腺癌（ADC）进展过程中的作用仍不清楚。通过免疫组织化学和形态计量学方法对88例ADC样本的Id - 1、2、3水平以及血管生成情况（CD34和VEGF微血管密度）进行了评估。对这些标志物在随访直至死亡或复发期间的影响进行了检测。发现肿瘤组织和正常组织在Id - 1、2、3表达上存在显著差异（P < 0.01）。此外，核内高水平的Id - 1与肿瘤间质中更高的血管生成相关（P < 0.01）。同样显著的是，T1期患者与细胞质低水平Id - 2相关，以及IIb期患者与低水平Id - 3相关。细胞质中高水平的Id - 3表达也与淋巴结转移直接相关（P = 0.05）。I - III期患者中，细胞质中Id - 1和Id - 3组织学评分低的患者比Id - 1或Id - 3高表达的患者无转移生存期显著更长（P = 0.04）。此外，与低表达的MVD - CD34和MVD - VEGF相比，高表达的MVD - CD34和MVD - VEGF与较短的无复发生存期相关（P = 0.04）。对年龄、淋巴结转移和辅助治疗进行控制的Cox模型分析表明，核内Id - 1、细胞质Id - 3和MVD - CD34与生存时间显著相关。核内Id - 1和细胞质Id - 3的中位评分将患者分为两组，Id - 1和Id - 3升高的患者死亡风险更高。Ids在肺腺癌患者中显示出独立的预后价值，与疾病分期无关。在肺腺癌的个性化治疗发展中，Id - 1和Id - 3应被视为新的潜在靶点。
Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.