水通道蛋白(AQP)通道能够调节水和溶质的运输,这是流体稳态所必需的。但它们作为抗癌疗法的靶点正受到关注。通过系统评价(PubMed和Embase)和RNAseq数据的转录组学分析(人蛋白质图谱数据库)评估患者的AQP表达和存活率的模式。荟萃分析证实AQP蛋白和RNA表达水平与患者生存时间之间主要呈负相关。最值得注意的是肺中的AQP1,乳腺癌和前列腺癌;AQP3在食管癌,肝癌和乳腺癌;AQP9在肝癌中的作用。AQP的表达模式聚集在癌症组中,并与死亡风险相关。在人类癌症活组织检查中AQP1-10的定量转录组分析类似地显示,AQP1、3、5和9的转录水平增加最常见地与低存活率相关。出乎意料的是,AQP7和AQP8水平升高与神经胶质瘤更好的生存时间相关,卵巢癌和子宫内膜癌,并增加AQP11,在结直肠癌和乳腺癌中具有更好的生存率。尽管水通道蛋白在病理或保护中的分子机制仍有待完全定义,此处的结果支持以下假设:选定AQPs类别的过表达差异增强了癌症进展.除了液体稳态,AQPs在癌症中的潜在作用(从对其在正常组织中的功能的扩大认识中提出)包括细胞运动性,膜过程扩展,信号分子的运输,增殖和凋亡的控制,增加机械合规性,和气体交换。AQP的表达也与化疗敏感性的差异有关。提示作为个性化治疗的生物标志物的可能作用。AQP药物调节剂的发展,以癌症特异性组合施用,可能会激发新的干预措施来控制恶性肿瘤。
Aquaporin (
AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of
AQP expression and survival rates for patients were evaluated by systematic
review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between
AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of
AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange.
AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.