Abstract
Pancreatic cancer (PC) is one of the most deadly cancers worldwide. To uncover the unknown novel biomarker used to indicate early diagnosis and prognosis in the molecular therapeutic field of PC is extremely of importance. Accumulative evidences indicated that aberrant expression or activation of immunoinhibitors is a common phenomenon in malignances, and significant associations have been noted between immunoinhibitors and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of immunoinhibitors contributing to tumorigenesis and progression of pancreatic cancer (PC) have not yet been elucidated clearly. In this study, we investigated the distinct expression and prognostic value of immunoinhibitors in patients with PC by analyzing a series of databases, including TISIDB, GEPIA, cBioPortal, and Kaplan-Meier plotter database. The mRNA expression levels of IDO1, CSF1R, VTCN1, KDR, LGALS9, TGFBR1, TGFB1, IL10RB, and PVRL2 were found to be significantly upregulated in patients with PC. Aberrant expression of TGFBR1, VTCN1, and LGALS9 was found to be associated with the worse outcomes of patients with PC. Bioinformatics analysis demonstrated that LGALS9 was involved in regulating the type I interferon signaling pathway, interferon-gamma-mediated signaling pathway, RIG-I-like receptor signaling pathway, NF-kappa B signaling pathway, cytosolic DNA-sensing pathway, and TNF signaling pathway. And TGFB1 was related to mesoderm formation, cell matrix adhesion, TGF-beta signaling pathway, and Hippo signaling pathway. These results suggested that LGALS9 and TGFBR1 might serve as potential prognostic biomarkers and targets for PC.
Highlights
The mortality of pancreatic cancer (PC), the fourth widely occurred cancer with poor prognosis, has an overall fiveyear survival rate lower than 10% [1]
The data demonstrated TGFB1 (Figure 2(a)), PVRL2 (Figure 2(b)), CSF1R (Figure 2(c)), TGFBR1 (Figure 2(d)), VTCN1 (Figure 2(e)), LGALS9 (Figure 2(f)), IL10RB (Figure 2(g)), KDR (Figure 2(h)), and IDO1 (Figure 2(i)) mRNA levels were significantly upregulated in patients with PC compared to normal tissues
We found that TGFB1 was related to mesoderm formation, cell matrix adhesion, substrate adhesion-dependent cell spreading, in utero embryonic development, extracellular matrix organization, outflow tract septum morphogenesis, mitral valve morphogenesis, and Hippo signaling (Figure 7(c))
Summary
The mortality of pancreatic cancer (PC), the fourth widely occurred cancer with poor prognosis, has an overall fiveyear survival rate lower than 10% [1]. The emergence of immune checkpoints inhibitors typically interfered negative regulators of T cell immunity including LAG3 [10,11,12], CTLA-4 [13, 14], PD-1 [15, 16], and TIM3 [17, 18]. The advent of these “checkpoint inhibitors” has thoroughly altered and improved the former therapies for melanoma, lung cancer, and so on [19]. Understanding the potential functions and expression pattern of immune “checkpoint inhibitors” could be helpful for the identification of novel prognosis and treatment biomarkers for PC
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