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Identification of solute carrier family genes related to the prognosis and tumor-infiltrating immune cells of pancreatic ductal adenocarcinoma.


ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) has persisted as one of the worst prognostic tumors with a 5-year survival rate of lower than 6%. Although many studies have investigated PDAC, new biomarkers are required to ensure early diagnosis and predict the prognosis of PDAC.

Methods

In this study, we used bioinformatics methods to evaluate differences in the expression of solute carrier (SLC) family genes in tumors and non-tumors. A Kaplan-Meier analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox proportional hazards regression analysis were used to evaluate the relationship between SLC genes and prognosis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic signature was constructed depending on the risk score to assess the impact of multiple genes on the prognosis, receiver operating characteristic (ROC) curves and forest plot was constructed to assess the ability to predict the prognosis and effects of clinical variables in both high- and low-risk groups. Tumor-infiltrating immune cells were evaluated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) in both high- and low-risk groups.

Results

In 32 SLC genes, 9 were significantly associated with the OS after LASSO analysis. SLC19A3 (P=0.007), SLC25A39 (P=0.027), SLC39A11 (P=0.043) were significantly associated with prognosis and included into the prognostic model. CIBERSORT demonstrated that memory B cells (P=0.004), naive B cells (P=0.007), CD8 T cells (P=0.003), activated memory CD4 T cells (P=0.004), and activated NK cells (P=0.019) were significantly higher in the low-risk group. Gene set enrichment analysis (GSEA) showed that potential molecular mechanisms enriched in MYC and p53 signaling pathways.

Conclusions

SLC19A3, SLC25A35, and SLC39A11 were significantly relative to the prognosis of PDAC and changed the tumor microenvironment, as well as the MYC and p53 signaling pathways. The SLC19A3 gene may represent a new tumor suppressor in PDAC.

SUBMITTER: Meng Y 

PROVIDER: S-EPMC8848431 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Identification of solute carrier family genes related to the prognosis and tumor-infiltrating immune cells of pancreatic ductal adenocarcinoma.

Meng Yuhua Y   Li Yanting Y   Fang Dalang D   Huang Yuanlu Y  

Annals of translational medicine 20220101 2


<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) has persisted as one of the worst prognostic tumors with a 5-year survival rate of lower than 6%. Although many studies have investigated PDAC, new biomarkers are required to ensure early diagnosis and predict the prognosis of PDAC.<h4>Methods</h4>In this study, we used bioinformatics methods to evaluate differences in the expression of solute carrier (SLC) family genes in tumors and non-tumors. A Kaplan-Meier analysis, least absolute sh  ...[more]

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