CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：High ANO1 expression is a prognostic factor and correlated with an immunosuppressive tumor microenvironment in pancreatic cancer.
High ANO1 expression is a prognostic factor and correlated with an immunosuppressive tumor microenvironment in pancreatic cancer.
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ANO1 是 PC 患者根治性切除后的预后因素。ANO1 可能以旁分泌方式在 PC 中诱导免疫抑制性肿瘤微环境，提示 ANO1 可能是一个新的治疗靶点。
氨基辛胺（ANO1）在多种癌症中发挥致癌作用。然而，其在胰腺癌（PC）中的作用鲜有研究。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。
连续纳入PC患者（n = 119）。采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（CAFs）中成纤维细胞活化蛋白（FAP）和α平滑肌肌动蛋白的表达，以及CD8阳性和FOXP3阳性TIL（肿瘤浸润淋巴细胞）（TILs）的数量。分析ANO1的预后价值及其与CAF亚群和TILs的相关性。利用癌症基因组图谱（TCGA）数据集预测ANO1在PC肿瘤微环境（TME）中的可能机制。
AN01的表达与总生存期（OS）和无病生存期相关。多因素分析显示，ANO1高表达是OS的独立不良预后因素（风险比，4.137；P = 0.001）。ANO1表达与CAFs中FAP的表达呈正相关（P < 0.001），与CD8阳性TILs数量呈负相关（P = 0.005），这一结果也在TCGA数据集的生物信息学分析中得到验证。此外，TCGA数据集的生物信息学分析揭示，ANO1可能通过旁分泌方式在胰腺癌中诱导免疫抑制性肿瘤微环境。
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.
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.
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.
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.
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