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

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

doi:10.3389/fmolb.2022.750083

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Highlights

DAAM2 participates in the oncogenesis and progression of human cancers
We first performed a pancancer analysis to investigate the immunological role of DAAM2 in all accessible tumor types in the TCGA database
DAAM2 expression was highly correlated with most types of tumor-infiltrating immune cells (TIICs) in most gastrointestinal tumors, such as COAD, ESCA, Pancreatic adenocarcinoma (PAAD) and READ (Figure 1B)

Summary

Introduction

DAAM2 participates in the oncogenesis and progression of human cancers. The role of DAAM2 in cancers has been preliminarily investigated, its correlations with antitumor immunity are unclear. Immunotherapy has emerged as a promising therapeutic strategy for PAAD (Banerjee et al, 2018). The response to immunotherapy largely depends on the tumor microenvironment (TME), which consists of immune cells, stromal cells, vascular networks, and many other cellular and noncellular components (Duan et al, 2020). Immuno-hot tumors are characterized by T cell infiltration and molecular signatures of immune activation and exhibit a higher response to various therapies, including immunotherapy (Duan et al, 2020). Potential biomarkers that could be used to identify tumor immunogenicity are significant for the demarcation of populations with advantages for immunotherapy

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Results

Discussion

Conclusion