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Qinglin Zhang,* He Nie,* Jiadong Pan, Haoran Xu, Qiang Zhan Department of Gastroenterology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinglin Zhang; Qiang Zhan, Email zhang517068@126.com; ryzhanqiang@163.comBackground: FMNL3 (Formin-like protein 3) is involved in the tumorigenesis of multiple cancers. The critical role of FMNL3 in malignancies has been preliminarily explored, but its immunological correlation is not clear.Methods: A pan-cancer analysis was performed to investigate the expressions, prognostic values, and immunological roles of FMNL3 across cancer types in The Cancer Genome Atlas (TCGA) database. Next, the correlations between FMNL3 and immunological features in the tumor microenvironment (TME) of pancreatic cancer (PAAD) were assessed. Besides, the role of FMNL3 in predicting the clinical characteristics and the responses to various therapies in PAAD was evaluated as well. Besides, the correlations between FMNL3 and the emerging immune-related biomarkers were also evaluated.Results: The pan-cancer analysis uncovered inconsistent expression status and prognostic values in several cancers. Besides, FMNL3 exhibited positive correlations with a majority of immunomodulators and tumor-infiltrating immune cells (TIICs) in several cancer types, including PAAD. In addition, FMNL3 was associated with an inflamed phenotype in the TME and predicted significantly higher responses to multiple anti-cancer therapies. In addition, FMNL3 was notably correlated with immune-related microbiota and N6-methyladenosine (m6A) genes.Conclusion: In summary, FMNL3 predicts an immuno-hot phenotype, which could be a promising indicator for identifying high immunogenicity in PAAD.Keywords: FMNL3, PAAD, tumor microenvironment, bioinformatics analysis, formin |