Molecular alterations in pancreatic tumors

Visani, Michela; Acquaviva, Giorgia; Leo, Antonio De; Sanza, Viviana; Merlo, Lidia; Maloberti, Thais; Brandes, Alba Ariela; Franceschi, Enrico; Battista, Monica Di; Masetti, Michele; Jovine, Elio; Fiorino, Sirio; Pession, Annalisa; Tallini, Giovanni; Biase, Dario de

doi:10.3748/wjg.v27.i21.2710

Cited by 20 publications

(16 citation statements)

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“…Structural variation, gene mutation and gene copy number alteration are important factors affecting gene expression and function, and are closely related to the activation of oncogenes or the inactivation of tumor suppressor genes ( Malhotra et al, 2013 ; Schaefer et al, 2019 ; Visani et al, 2021 ). The results of pan-cancer analysis showed that the USP45 gene had a low frequency of structural variants, mainly present in PRAD and LIHC ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer

Wang

Bian

et al. 2022

Front. Mol. Biosci.

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Background: Deubiquitinating enzymes specifically removes ubiquitin molecules from ubiquitin-tagged target proteins, thereby inhibiting the degradation of target proteins and playing an important role in tumor. However, the mechanism of deubiquitinating enzyme USP45 in tumors remains unclear.Methods: Based on the RNA-seq data of tissues and cell lines in The Cancer Genome Atlas (TCGA) database, GTEx and CCLE database, the pan-cancer analysis of USP45 expression and survival outcome were performed using R software and Kaplan-Meier Plotter. The structural variants, gene mutations and gene copy number alteration of USP45 were analyzed using the TCGA Pan-Cancer Atlas Studies dataset in the cBioPortal database. The relationships between USP45 and mRNA methylation, tumor heterogeneity, tumor stemness, and tumor immunity were performed by Sangerbox platform and TIMER2.0 using Pearson correlation analysis. Through the ENCORI database and string database, we constructed the ceRNA regulatory mechanism and protein-protein interaction network for USP45. Based on the RNA-seq data in TCGA and GTEx databases, we also constructed the downstream regulatory network for USP45 using the Limma and ClusterProfiler packages of R software. At last, the protein expression levels of USP45 were detected by immunohistochemistry in tumor tissue microarrays.Results: USP45 is upregulated in most types of tumors and negatively correlated with the overall survival and recurrence-free survival of patient. Furthermore, the structural variation, gene mutations and gene copy number variation of USP45 were identified in different types of tumors. The pan-cancer analysis showed that USP45 was closely related to mRNA methylation, tumor heterogeneity and tumor stemness. In most types of tumors, the expression of USP45 was positively correlated with many immune checkpoint molecules and immune regulators such as PD-L1, while negatively correlated with the infiltration levels of NK cells, Th1 cells, macrophages, and dendritic cells in the tumor microenvironment. Finally, we constructed the ceRNA regulatory network, protein-protein interaction network and downstream regulatory network for USP45 in different types of tumors.Conclusion: Our study firstly explored the putative oncogenic role of USP45 in pan-cancer, and provided insights for further investigation of USP45.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer

Wang

Bian

et al. 2022

Front. Mol. Biosci.

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“…19 Pancreas cancers are often associated with molecular alterations in the KRAS, TP53, CDKN2A/CDKN2B, BRCA, and SMAD4 genes. 20 Cholangiocarcinoma is an aggressive hepatobiliary neoplasm arising from bile ducts in the liver. There are three main types of cholangiocarcinoma: intrahepatic, perihilar, and extrahepatic.…”

Section: Pathologist Discussionmentioning

confidence: 99%

Carcinoma of unknown primary: Molecular tumor board‐based therapy

Shreenivas

Kato

et al. 2022

CA A Cancer J Clinicians

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“…At this time, risk factors associated with the development of PDAC was not clearly established although classical risk factors were suggested as smoking, obesity, age and inflammation ( 81 ). As most cancers, epigenetic and genetic deregulation were observed as Kras mutation observed in >90% for PDAC ( 82 ). PDAC was a very aggressive cancer which rapidly induced metastasis associated to the poor prognosis of this cancer ( 79 ).…”

Section: Anti-tumoral Properties Of Orexins and Receptor Antagonist A...mentioning

confidence: 99%

The Orexin receptors: Structural and anti-tumoral properties

et al. 2022

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At the end of the 20th century, two new neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) expressed in hypothalamus as a prepro-orexins precursor, were discovered. These two neuropeptides interacted with two G protein-coupled receptor isoforms named OX1R and OX2R. The orexins/OX receptors system play an important role in the central and peripheral nervous system where it controls wakefulness, addiction, reward seeking, stress, motivation, memory, energy homeostasis, food intake, blood pressure, hormone secretions, reproduction, gut motility and lipolysis. Orexins and their receptors are involved in pathologies including narcolepsy type I, neuro- and chronic inflammation, neurodegenerative diseases, metabolic syndrome, and cancers. Associated with these physiopathological roles, the extensive development of pharmacological molecules including OXR antagonists, has emerged in association with the determination of the structural properties of orexins and their receptors. Moreover, the identification of OX1R expression in digestive cancers encompassing colon, pancreas and liver cancers and its ability to trigger mitochondrial apoptosis in tumoral cells, indicate a new putative therapeutical action of orexins and paradoxically OXR antagonists. The present review focuses on structural and anti-tumoral aspects of orexins and their receptors.

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Molecular alterations in pancreatic tumors

Cited by 20 publications

References 131 publications

Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer

Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer

Carcinoma of unknown primary: Molecular tumor board‐based therapy

The Orexin receptors: Structural and anti-tumoral properties

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