Dataset Information

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

ABSTRACT:

Background

Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets.

Methods

Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed for functional modules analysis and identification of hub genes. qRT-PCR of clinical samples was conducted to validate the expression level of the hub genes.

Results

A total of 110 DEGs were identified from our RNA-seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out five hub genes including IL-6, LCN2, FABP4, LEP and MMP1, which were identified as core genes in the network and the expression value were validated by qRT-PCR. The hub genes identified in this work were suggested to be potential therapeutic targets of DPC.

Discussion

The current study may provide new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.

SUBMITTER: Lu Y

PROVIDER: S-EPMC7789135 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

Lu Yuanxiang Y Li Wensen W Liu Ge G Yang Yongbo Y Xiao Erwei E Mu Senmao S Guo Yuqi Y Li Deyu D Yan Guoyi G

Cancer cell international 20210106 1

<h4>Background</h4>Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets.<h4>Methods</h4>Tumor samples of three DPC patients were collected and integrating RNA ...[more]

PMID: 33407508

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Project description:BACKGROUND: Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. METHODS: Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip(R) Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. RESULTS: The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-beta, activin, their receptors and Smad3, as well as the Notch ligands and members of the gamma-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of beta-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. CONCLUSION: At least six metabolic pathways support the morphological and functional differences between carcinomas and papillary adenocarcinomas. Differential gene-expression profiles favor cell adhesion, motility and proliferation in the carcinoma. Cell-cell contact, polarity, earlier cell-cycle arrest and DNA damage control are better displayed in the papillary adenocarcinoma.

Dataset Information

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

Background

Methods

Results

Discussion

Publications

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

Similar Datasets

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