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形态发生相关紊乱激活因子2(DAAM2)预测胰腺腺癌的免疫热表型。

Dishevelled-Associated Activator of Morphogenesis 2 (DAAM2) Predicts the Immuno-Hot Phenotype in Pancreatic Adenocarcinoma.

作者信息

Zhang Qinglin, Pan Jiadong, Nie He, Wang Hui, An Fangmei, Zhan Qiang

机构信息

Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

出版信息

Front Mol Biosci. 2022 Feb 24;9:750083. doi: 10.3389/fmolb.2022.750083. eCollection 2022.

Abstract

DAAM2 participates in the oncogenesis and progression of human cancers. Although the role of DAAM2 in cancers has been preliminarily investigated, its correlations with antitumor immunity are unclear. A pancancer analysis was conducted to explore the immunological role of DAAM2 based on RNA sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between DAAM2 and immunological characteristics in the tumor microenvironment (TME) of pancreatic adenocarcinoma (PAAD) were evaluated. In addition, the role of DAAM2 in predicting the clinical characteristics and the response to various therapies in PAAD were also assessed. In addition, the correlations between DAAM2 and the emerging immunobiomarker N6-methyladenosine (m6A) genes were also evaluated. Pancancer analysis revealed that DAAM2 exhibited positive correlations with a majority of immunomodulators, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints in several cancer types, including PAAD. In addition, DAAM2 was associated with an inflamed phenotype in the tumor microenvironment (TME). DAAM2 also predicted significantly higher responses to chemotherapy, anti-EGFR therapy and immunotherapy but lower responses to anti-ERBB2 and antiangiogenic therapy. In addition, DAAM2 was correlated with immune-related microbiota. In PAAD DAAM2 is associated with an immuno-hot phenotype and can help predict the outcome of various therapeutic options. Overall, DAAM2 is a promising indicator for assessing high immunogenicity in PAAD.

摘要

DAAM2参与人类癌症的发生和发展。尽管已对DAAM2在癌症中的作用进行了初步研究,但其与抗肿瘤免疫的相关性尚不清楚。基于从癌症基因组图谱(TCGA)下载的RNA测序(RNA-seq)数据进行了泛癌分析,以探索DAAM2的免疫作用。接下来,评估了DAAM2与胰腺腺癌(PAAD)肿瘤微环境(TME)中免疫特征的相关性。此外,还评估了DAAM2在预测PAAD临床特征和对各种疗法反应方面的作用。此外,还评估了DAAM2与新兴免疫生物标志物N6-甲基腺苷(m6A)基因之间的相关性。泛癌分析显示,在包括PAAD在内的几种癌症类型中,DAAM2与大多数免疫调节剂、肿瘤浸润免疫细胞(TIICs)和抑制性免疫检查点呈正相关。此外,DAAM2与肿瘤微环境(TME)中的炎症表型相关。DAAM2还预测对化疗、抗EGFR治疗和免疫治疗的反应显著更高,但对抗ERBB2和抗血管生成治疗的反应更低。此外,DAAM2与免疫相关微生物群有关。在PAAD中,DAAM2与免疫热表型相关,有助于预测各种治疗选择的结果。总体而言,DAAM2是评估PAAD高免疫原性的一个有前景的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9094/8907973/5ebafab58cbd/fmolb-09-750083-g001.jpg

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