Chen Guo, Song Haiyang, Yang Zelong, Du Tianshu, Zheng Yu, Lu Zifan, Zhang Kunpeng, Wei Di
Department of Biopharmaceuticals, School of Pharmacy, Air Force Medical University, Xi'an, China.
Department of Interventional Therapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Front Oncol. 2022 May 10;12:890193. doi: 10.3389/fonc.2022.890193. eCollection 2022.
Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with a poor prognosis. The identification of effective molecular markers is of great significance for diagnosis and treatment. Aquaporins (AQPs) are a family of water channel proteins that exhibit several properties and play regulatory roles in human carcinogenesis. However, the association between Aquaporin-5 (AQP5) expression and prognosis and tumor-infiltrating lymphocytes in PAAD has not been reported.
AQP5 mRNA expression, methylation, and protein expression data in PAAD were analyzed using GEPIA, UALCAN, HAP, METHSURV, and UCSC databases. AQP5 expression in PAAD patients and cell lines from our cohort was examined using immunohistochemistry and Western blotting. The LinkedOmics database was used to study signaling pathways related to AQP5 expression. TIMER and TISIDB were used to analyze correlations among AQP5, tumor-infiltrating immune cells, and immunomodulators. Survival was analyzed using TCGA and Kaplan-Meier Plotter databases.
In this study, we investigated AQP5 expression in PAAD and determined whether the expression of AQP5 is a strong prognostic biomarker for PAAD. We searched and analyzed public cancer databases (GEO, TCGA, HAP, UALCAN, GEPIA, etc.) to conclude that AQP5 expression levels were upregulated in PAAD. Kaplan-Meier curve analysis showed that high AQP5 expression positively correlated with poor prognosis. Using TIMER and TISIDB, we found that the expression of AQP5 was associated with different tumor-infiltrating immune cells, especially macrophages. We found that hypomethylation of the AQP5 promoter region was responsible for its high expression in PAAD.
AQP5 can serve as a novel biomarker to predict prognosis and immune infiltration in PAAD.
胰腺腺癌（PAAD）是一种预后较差的高度恶性肿瘤。鉴定有效的分子标志物对诊断和治疗具有重要意义。水通道蛋白（AQPs）是一类水通道蛋白家族，具有多种特性并在人类肿瘤发生中发挥调节作用。然而，水通道蛋白5（AQP5）表达与PAAD预后及肿瘤浸润淋巴细胞之间的关联尚未见报道。
使用GEPIA、UALCAN、HAP、METHSURV和UCSC数据库分析PAAD中AQP5 mRNA表达、甲基化和蛋白质表达数据。通过免疫组织化学和蛋白质印迹法检测我们队列中PAAD患者和细胞系中AQP5的表达。使用LinkedOmics数据库研究与AQP5表达相关的信号通路。使用TIMER和TISIDB分析AQP5、肿瘤浸润免疫细胞和免疫调节剂之间的相关性。使用TCGA和Kaplan-Meier Plotter数据库分析生存率。
在本研究中，我们调查了PAAD中AQP5的表达，并确定AQP5的表达是否是PAAD的一个强有力的预后生物标志物。我们搜索并分析了公共癌症数据库（GEO、TCGA、HAP、UALCAN、GEPIA等），得出PAAD中AQP5表达水平上调的结论。Kaplan-Meier曲线分析表明，高AQP5表达与不良预后呈正相关。使用TIMER和TISIDB，我们发现AQP5的表达与不同的肿瘤浸润免疫细胞相关，尤其是巨噬细胞。我们发现AQP5启动子区域的低甲基化是其在PAAD中高表达的原因。
AQP5可作为预测PAAD预后和免疫浸润的新型生物标志物。
