Bellezza Guido, Vannucci Jacopo, Bianconi Fortunato, Metro Giulio, Del Sordo Rachele, Andolfi Marco, Ferri Ivana, Siccu Paola, Ludovini Vienna, Puma Francesco, Sidoni Angelo, Cagini Lucio
Section of Anatomic Pathology and Histology, Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy.
Department of Thoracic Surgery, University of Perugia Medical School, Perugia, Italy.
Interact Cardiovasc Thorac Surg. 2017 Dec 1;25(6):856-861. doi: 10.1093/icvts/ivx202.
Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients.
Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed.
AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001).
Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC.
水通道蛋白（AQPs）是一类跨膜水选择性通道蛋白，被认为在调节质膜水通透性中发挥作用。事实上，已有研究表明高AQP水平会促进肿瘤的进展、侵袭和转移。具体而言，肺腺癌（AC）中AQP1和AQP5的过表达被认为与肺癌的分子机制有关。这项回顾性队列单中心研究的目的是评估AQP1和AQP5在接受手术切除的AC患者中的表达水平及其预后意义。
本队列研究纳入了经组织学诊断为肺AC并接受肺切除术的患者。制备了包含185个AC样本芯块的组织微阵列。通过免疫组织化学评估AQP1和AQP5的表达。结果分为低表达（评分0 - 2）或高表达（评分3 - 9）。记录临床数据、病理肿瘤-淋巴结-转移分期和随访情况。进行多变量Cox生存分析和Fisher t检验。
85例（46%）患者检测到AQP1过表达，45例（24%）患者观察到AQP5过表达。AQP1与临床和病理参数无显著相关性，而AQP5在黏液性和乳头状为主型的AC中表达更高。与未过表达AQP1的患者相比，过表达AQP1的患者无病生存期较短（P = 0.001）。多变量分析证实AQP1过表达与较短的无病生存期显著相关（P = 0.001）。
我们的结果表明，AQP1过表达导致肺AC患者无病生存期缩短。因此，AQP1过表达可能是肺AC的一个重要预后标志物。
