ANO1 高表达是胰腺癌的一个预后因素，并与免疫抑制性肿瘤微环境相关。
High ANO1 expression is a prognostic factor and correlated with an immunosuppressive tumor microenvironment in pancreatic cancer.
机构信息
Department of Hepatobiliary Surgery and Center of Severe Acute Pancreatitis, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Department of Organ Transplantation, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
出版信息
Front Immunol. 2024 Jan 30;15:1341209. doi: 10.3389/fimmu.2024.1341209. eCollection 2024.
BACKGROUND
Aminooctylamine (ANO1) plays an oncogenic role in various cancers. However. its role in pancreatic cancer (PC) has rarely been studied. This study investigated the prognostic value of ANO1 and its correlation with the tumor microenvironment (TME) in PC.
METHODS
Consecutive patients with PC (n = 119) were enrolled. The expression of ANO1 in cancer cells, the expression of fibroblast activation protein (FAP) and alpha smooth muscle actin in cancer-associated fibroblasts (CAFs), and the numbers of CD8- and FOXP3-positive tumor-infiltrating lymphocytes (TILs) were evaluated using immunohistochemistry. The prognostic value of ANO1 and its correlation with CAF subgroups and TILs were analyzed. The possible mechanism of ANO1 in the TME of PC was predicted using the the Cancer Genome Atlas (TCGA) dataset.
RESULTS
The expression of AN01 was correlated with overall survival (OS) and disease-free survival. Multi-factor analysis showed that high ANO1 expression was an independent adverse prognostic factor for OS (hazard ratio, 4.137; P = 0.001). ANO1 expression was positively correlated with the expression of FAP in CAFs (P < 0.001) and negatively correlated with the number of CD8-positive TILs (P = 0.005), which was also validated by bioinformatics analysis in the TCGA dataset. Moreover, bioinformatic analysis of the TCGA dataset revealed that ANO1 may induce an immunosuppressive tumor microenvironment in pancreatic cancer in a paracrine manner.
CONCLUSION
ANO1 is a prognostic factor in patients with PC after radical resection. ANO1 may induce an immunosuppressive tumor microenvironment in PC in a paracrine manner, suggesting that ANO1 may be a novel therapeutic target.
背景
氨甲辛胺（ANO1）在多种癌症中发挥致癌作用。然而，其在胰腺癌（PC）中的作用很少被研究。本研究探讨了ANO1在 PC 中的预后价值及其与肿瘤微环境（TME）的相关性。
方法
连续纳入 119 例 PC 患者。使用免疫组织化学方法评估癌细胞中 ANO1 的表达、癌相关成纤维细胞（CAF）中成纤维细胞激活蛋白（FAP）和α平滑肌肌动蛋白的表达以及 CD8-和 FOXP3-阳性肿瘤浸润淋巴细胞（TIL）的数量。分析 ANO1 的预后价值及其与 CAF 亚群和 TIL 的相关性。使用癌症基因组图谱（TCGA）数据集预测 ANO1 在 PC 的 TME 中的可能机制。
结果
ANO1 的表达与总生存期（OS）和无病生存期相关。多因素分析显示，高 ANO1 表达是 OS 的独立不良预后因素（风险比，4.137；P = 0.001）。ANO1 表达与 CAF 中 FAP 的表达呈正相关（P < 0.001），与 CD8-阳性 TIL 的数量呈负相关（P = 0.005），这在 TCGA 数据集的生物信息学分析中也得到了验证。此外，TCGA 数据集的生物信息学分析表明，ANO1 可能以旁分泌方式诱导胰腺癌中的免疫抑制肿瘤微环境。
结论
ANO1 是根治性切除术后 PC 患者的预后因素。ANO1 可能以旁分泌方式诱导 PC 中的免疫抑制肿瘤微环境，提示 ANO1 可能是一种新的治疗靶点。
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