Abstract
Yes-associated protein-1 (YAP1) is an important effector of the Hippo pathway and has crosstalk with other cancer signaling pathways. It induces an immunosuppressive tumor microenvironment by activating pathways in several cellular components. However, the mechanisms by which it drives immune infiltration in pancreatic cancer remain poorly understood. We analyzed the expression of YAP1 as well as its prognostic value and correlations with immune infiltrates in various cancers, with a focus on pancreatic cancer. In particular, using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA) database, we found that YAP1 is differentially expressed between tumor tissues and control tissues in a number of cancers and in particular, is elevated in pancreatic cancer. Using the Kaplan–Meier plotter, GEPIA, and Long-term Outcome and Gene Expression Profiling database of pan-cancers (LOGpc), we further established the prognostic value of YAP1. We found that YAP1 expression was significantly related to outcomes in multiple types of cancer based on data from The Cancer Genome Atlas, particularly in pancreatic cancer. Correlations between YAP1 and immune cell infiltration and immune cell marker expression were examined using Tumor Immune Estimation Resource and GEPIA. High expression levels of YAP1 were significantly associated with a variety of immune markers and immune cell subsets in pancreatic cancer. These results suggest that YAP1 is correlated with patient outcomes and tumor immune cell infiltration in multiple cancer types and is a valuable prognostic biomarker in pancreatic cancer.
Highlights
Pancreatic cancer is the fifth most common cause of cancer-related deaths in developed countries, accounting for 260,000 deaths worldwide every year; its 5-years survival rate is extremely low (5%) (Johansson et al, 2016)
Using the TCGA and TIMER databases, Yes-associated protein-1 (YAP1) expression was significantly lower in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), and uterine corpus endometrial carcinoma (UCEC) than in adjacent normal tissues
Using Gene Expression Profiling Interactive Analysis (GEPIA) databases, the expression of YAP1 was significantly higher in tumor tissues than in normal controls in CHOL, Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), Glioblastoma multiforme (GBM), Pancreatic
Summary
Pancreatic cancer is the fifth most common cause of cancer-related deaths in developed countries, accounting for 260,000 deaths worldwide every year; its 5-years survival rate is extremely low (5%) (Johansson et al, 2016). Since immunotherapy was declared a breakthrough approach in 2013, the effectiveness of immune checkpoint inhibition has been demonstrated in various solid tumors, and it may be beneficial in pancreatic cancer (Gan et al, 2020). Clinical studies of immunotherapy for pancreatic cancer are ongoing (Zhang and Choi, 2015; Martinez-Bosch et al, 2018), and the characterization of immunophenotypes and identification of novel immune-related therapeutic targets in pancreatic cancer are urgent research goals (Luedke et al, 2012). YAP1 in cancer cells confers resistance to certain drugs (Zhou et al, 2018; Yao et al, 2019)
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