Classification and Prognosis Analysis of Pancreatic Cancer Based on DNA Methylation Profile and Clinical Information

Li, Xin; Zhang, Xuan; Lin, Xiangyu; Cai, Lei; Wang, Yan; Chang, Zhiqiang

doi:10.3390/genes13101913

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Genomic and epigenetic modifications such as DNA methylation can result in dysregulated gene expression, which can affect clinical outcomes in pancreatic cancer (X Li et al 2022b ). Figure 3 A illustrates a pan-cancer overview of the deleterious mutations analyzed using GSCA.…”

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Zheng

et al. 2023

Funct Integr Genomics

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Contribution of integrin superfamily genes to treatment resistance remains uncertain. Genome patterns of thirty integrin superfamily genes were analyzed of using bulk and single-cell RNA sequencing, mutation, copy number, methylation, clinical information, immune cell infiltration, and drug sensitivity data. To select the integrins that are most strongly associated with treatment resistance in pancreatic cancer, a purity-independent RNA regulation network including integrins were constructed using machine learning. The integrin superfamily genes exhibit extensive dysregulated expression, genome alterations, epigenetic modifications, immune cell infiltration, and drug sensitivity, as evidenced by multi-omics data. However, their heterogeneity varies among different cancers. After constructing a three-gene (TMEM80, EIF4EBP1, and ITGA3) purity-independent Cox regression model using machine learning, ITGA3 was identified as a critical integrin subunit gene in pancreatic cancer. ITGA3 is involved in the molecular transformation from the classical to the basal subtype in pancreatic cancer. Elevated ITGA3 expression correlated with a malignant phenotype characterized by higher PD-L1 expression and reduced CD8+ T cell infiltration, resulting in unfavorable outcomes in patients receiving either chemotherapy or immunotherapy. Our findings suggest that ITGA3 is an important integrin in pancreatic cancer, contributing to chemotherapy resistance and immune checkpoint blockade therapy resistance. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Zheng

et al. 2023

Funct Integr Genomics

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“…Aberrant DNA methylation has also been proposed as a prognostic marker for pancreatic cancer. Alterations in the promoter methylation level of genes affect the transcription of oncogenes and tumor suppressors, thus regulating tumorigenesis [ 49 ]. We therefore checked whether PTGES-regulated transcriptional changes are regulated by DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

PTGES Expression Is Associated with Metabolic and Immune Reprogramming in Pancreatic Ductal Adenocarcinoma

Murthy

Attri

2023

IJMS

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Metabolic reprogramming is an established hallmark of multiple cancers, including pancreatic cancer. Dysregulated metabolism is utilized by cancer cells for tumor progression, metastasis, immune microenvironment remodeling, and therapeutic resistance. Prostaglandin metabolites have been shown to be critical for inflammation and tumorigenesis. While the functional role of prostaglandin E2 metabolite has been extensively studied, there is a limited understanding of the PTGES enzyme in pancreatic cancer. Here, we investigated the relationship between expression of prostaglandin E synthase (PTGES) isoforms and the pathogenesis and regulation of pancreatic cancer. Our analysis identified higher expression of PTGES in pancreatic tumors compared to normal pancreatic tissues, suggesting an oncogenic function. Only PTGES1 expression was significantly correlated with worse prognosis of pancreatic cancer patients. Further, utilizing cancer genome atlas data, PTGES was found to be positively correlated with epithelial-mesenchymal transition, metabolic pathways, mucin oncogenic proteins, and immune pathways in cancer cells. PTGES expression was also correlated with higher mutational burden in key driver genes, such as TP53 and KRAS. Furthermore, our analysis indicated that the oncogenic pathway controlled by PTGES1 could be regulated via DNA methylation-dependent epigenetic mechanisms. Notably, the glycolysis pathway was positively correlated with PTGES and may fuel cancer cell growth. PTGES expression was also associated with downregulation of the MHC pathway and negatively correlated with CD8+ T cell activation markers. In summary, our study established an association of PTGES expression with pancreatic cancer metabolism and the immune microenvironment.

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“…Cluster2 was shown to be linked with a more favorable prognosis than Cluster1, which was found to be more common. Fourteen methylation genes that are exclusive to each PAAD subtype were found, and these genes might be used as molecular markers to describe the different methylation patterns that are associated with the two PAAD subtypes [ 48 ]. However, the DNA methylation signature of m6A regulators has not been investigated in the prognostic prediction of PC.…”

Section: Discussionmentioning

confidence: 99%

Identification of a New m6A Regulator-Related Methylation Signature for Predicting the Prognosis and Immune Microenvironment of Patients with Pancreatic Cancer

Zou

Shi

Wang

et al. 2023

Mediators of Inflammation

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Pancreatic cancer (PC) is a malignant tumor of the digestive system that has a bad prognosis. N6-methyladenosine (m6A) is involved in a wide variety of biological activities due to the fact that it is the most common form of mRNA modification in mammals. Numerous research has accumulated evidence suggesting that a malfunction in the regulation of m6A RNA modification is associated with various illnesses, including cancers. However, its implications in PC remain poorly characterized. The methylation data, level 3 RNA sequencing data, and clinical information of PC patients were all retrieved from the TCGA datasets. Genes associated with m6A RNA methylation were compiled from the existing body of research and made available for download from the m6Avar database. The LASSO Cox regression method was used to construct a 4-gene methylation signature, which was then used to classify all PC patients included in the TCGA dataset into either a low- or high-risk group. In this study, based on the set criteria of cor > 0.4 and p value < 0.05. A total of 3507 gene methylation were identified to be regulated by m6A regulators. Based on the univariate Cox regression analysis and identified 3507 gene methylation, 858 gene methylation was significantly associated with the patient’s prognosis. The multivariate Cox regression analysis identified four gene methylation (PCSK6, HSP90AA1, TPM3, and TTLL6) to construct a prognosis model. Survival assays indicated that the patients in the high-risk group tend to have a worse prognosis. ROC curves showed that our prognosis signature had a good prediction ability on patient survival. Immune assays suggested a different immune infiltration pattern in patients with high- and low-risk scores. Moreover, we found that two immune-related genes, CTLA4 and TIGIT, were downregulated in high-risk patients. We generated a unique methylation signature that is related to m6A regulators and is capable of accurately predicting the prognosis for patients with PC. The findings might prove useful for therapeutic customization and the process of making medical decisions.

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Classification and Prognosis Analysis of Pancreatic Cancer Based on DNA Methylation Profile and Clinical Information

Cited by 6 publications

References 35 publications

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

PTGES Expression Is Associated with Metabolic and Immune Reprogramming in Pancreatic Ductal Adenocarcinoma

Identification of a New m6A Regulator-Related Methylation Signature for Predicting the Prognosis and Immune Microenvironment of Patients with Pancreatic Cancer

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