Dataset Information

The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.

ABSTRACT: Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality rates. The NT5DC family is an evolutionarily-conserved family of 5'-nucleosidases that catalyze the intracellular hydrolysis of nucleotides. Although the NT5DC family has been linked to the initiation and growth of several cancers, its function in PAAD remains unclear. A series of bioinformatic analyses was used to ascertain the expression, prognosis, gene changes, functional enrichment, and immune regulatory functions of the NT5DC family in PAAD. NT5C2 and NT5DC1/2 mRNA and protein levels are increased in PAAD. Furthermore, the high mRNA expressions of NT5C2, NT5DC2, and NT5DC4 indicate a poor prognosis in patients with PAAD. The enrichment of biological processes and gene expression in the NT5DC family in PAAD were investigated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Further investigations into immune infiltration revealed a close relationship between NT5DC gene expression and immune cell infiltration. These findings provide new insights into the biological function and prognostic value of the NT5DC gene family in PAAD.

SUBMITTER: Yu X

PROVIDER: S-EPMC10414034 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.

Yu Xiaoqian X Sun Ru R Yang Xuejie X He Xiaoyun X Guo Hongbin H Ou Chunlin C

Journal of Cancer 20230716 12

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality rates. The NT5DC family is an evolutionarily-conserved family of 5'-nucleosidases that catalyze the intracellular hydrolysis of nucleotides. Although the NT5DC family has been linked to the initiation and growth of several cancers, its function in PAAD remains unclear. A series of bioinformatic analyses was used to ascertain the expression, prognosis, gene changes, functional enrichment, and immune regulatory ...[more]

PMID: 37576396

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Project description:BackgroundAll YTH domain family members are m6A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated.MethodsGEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database.ResultsmRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26%, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD.ConclusionThe molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD.

Project description:Background: Pancreatic adenocarcinoma (PAAD) has a high degree of malignancy and a very poor prognosis, and the 5-year overall survival rate of patients is approximately 7%. To improve the prognosis of patients with PAAD, a more comprehensive and in-depth study of the pathogenesis of PAAD and the identification of new diagnostic markers and treatment targets are urgently needed. Increasing evidence supports that the small ubiquitin-like modifier (SUMO) family is closely related to the occurrence and development of a variety of cancers. However, the function of the SUMO family in PAAD is not clear, and related research is very scarce. Methods: R, Cytoscape, cBioPortal, and other software and online databases were used to comprehensively analyze the expression characteristics, prognostic value, and oncogenic mechanism of the SUMO family in PAAD. Results: SUMO family members are highly expressed in PAAD, and high expression of SUMO family members is significantly associated with poor clinicopathological features and poor prognosis in PAAD patients. In addition, SUMO family members are significantly coexpressed with M6A methylation regulators and various oncogenes and play an activating role in various oncogenic pathways, including EMT. Furthermore, it is worth noting that the close association between SUMO family members and TP53 mutation status and the negative regulatory effect of SUMO1/2 on PAAD immunity may represent the potential mechanism by which SUMO family members promote the development of PAAD. Moreover, the coexpression characteristics of SUMO family members and a variety of cancer-promoting immune checkpoint genes, as well as the positive correlation between SUMO4 expression level and the sensitivity of various targeted or chemotherapeutic drugs, including gemcitabine, paclitaxel, and doxorubicin, suggest future clinical directions of this study. Conclusion: The SUMO family is closely related to the occurrence and development of PAAD and can be used as a new biomarker and therapeutic target for patients with PAAD.

Project description:BACKGROUND: p27(kip1) is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27(kip1) expression in adenocarcinoma of the pancreatic head region. PATIENTS AND METHODS: The study included 45 patients (male/female ratio 2:1; mean age 59, range 38-82 years) with adenocarcinomas of the pancreatic head region: 24 - pancreatic head, 18 - periampullary and 3 - uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27(kip1) expression was based on the proportion of p27(kip1) -positive cells (< 5% = negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. RESULTS: Positive p27(kip1) expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27(kip1)-negative. There were no significant correlations between p27(kip1) index and stage or lymph node involvement. Median survival time in patients with p27(kip1)-positive tumours was 19 months, whereas in patients with p27(kip1)-negative tumours it was 18 months (p=0.53). A significant relationship was found between p27(kip1)-negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p = 0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). CONCLUSION: We conclude that p27(kip1) has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed.

Dataset Information

The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.

Publications

The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.

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