ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer

Yu, Pian; Luo, Shifu; Cai, Jiaxin; Li, Jie; Peng, Cong

doi:10.18632/aging.204324

Cited by 4 publications

(9 citation statements)

References 40 publications

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“…The occurrence of thrombocytopenia was a positive prognostic marker for progression‐free survival, but myelosuppression had neither positive nor negative linkage to survival in this setting 173 . Another example of a potential immune‐related biomarker is endoplasmic reticulum aminopeptidase 2 (ERAP2), which correlates with worse prognosis in pancreatic cancer patients and its expression in pancreatic cancer cells is increased by gemcitabine treatment 177 . ERAP2 is a protein involved in the processing of peptide ligands for binding to MHC‐I, 178 but it also has a role in the PI3K/AKT/mTOR pathway, and whether its immunological function and/or its cell signaling function is the rationale for its correlation with poor prognosis is not well understood.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…173 Another example of a potential immune-related biomarker is endoplasmic reticulum aminopeptidase 2 (ERAP2), which correlates with worse prognosis in pancreatic cancer patients and its expression in pancreatic cancer cells is increased by gemcitabine treatment. 177 ERAP2 is a protein involved in the processing of peptide ligands for binding to MHC-I, 178 but it also has a role in the PI3K/AKT/mTOR pathway, and whether its immunological function and/or its cell signaling function is the rationale for its correlation with poor prognosis is not well understood. Bauer et al showed that gemcitabine therapy decreased DC vaccine impact on B cell and CD8 + T cell responses, but the combination of the DC vaccine and gemcitabine still was clinically beneficial, 179 showing the difficulty of establishing specific immunological biomarkers that correlate with overall clinical prowess.…”

Section: Perspectivesmentioning

confidence: 99%

“…Various investigations have sought biomarker correlates of gemcitabine treatment and patient outcomes, 175,176 and some studies have included hematological and immunological factors. 173,177 For example, Blomstrand et al profiled blood proteins and cells in pancreatic cancer patients and evaluated whether any were prognostic for prolonged survival. 173 The occurrence of thrombocytopenia was a positive prognostic marker for progressionfree survival, but myelosuppression had neither positive nor negative linkage to survival in this setting.…”

Section: Perspectivesmentioning

confidence: 99%

See 3 more Smart Citations

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

Larson,

Doty,

Solheim

2024

Cancer Medicine

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Although the development of immunotherapies has been revolutionary in the treatment of several cancers, many cancer types remain unresponsive to immune‐based treatment and are largely managed by chemotherapy drugs. However, chemotherapeutics are not infallible and are frequently rendered ineffective as resistance develops from prolonged exposure. Recent investigations have indicated that some chemotherapy drugs have additional functions beyond their normative cytotoxic capacity and are in fact immune‐modifying agents. Of the pharmaceuticals with identified immune‐editing properties, gemcitabine is well‐studied and of interest to clinicians and scientists alike. Gemcitabine is a chemotherapy drug approved for the treatment of multiple cancers, including breast, lung, pancreatic, and ovarian. Because of its broad applications, relatively low toxicity profile, and history as a favorable combinatory partner, there is promise in the recharacterization of gemcitabine in the context of the immune system. Such efforts may allow the identification of suitable immunotherapeutic combinations, wherein gemcitabine can be used as a priming agent to improve immunotherapy efficacy in traditionally insensitive cancers. This review looks to highlight documented immunomodulatory abilities of one of the most well‐known chemotherapy agents, gemcitabine, relating to its influence on cells and proteins of the immune system.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

Larson,

Doty,

Solheim

2024

Cancer Medicine

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“…Accumulating evidence suggests that ERAP2 is tractable targets for the regulation of immune responses [ 68 ]. In pancreatic cancer cells, gemcitabine could increase the mRNA and protein levels of ERAP2 [ 69 ]. However, no drugs targeted ERAP2 in CD yet.…”

Section: Heterogeneity Of Various Tissue Types Selected In Eqtlmentioning

confidence: 99%

Transcriptome-wide association studies associated with Crohn’s disease: challenges and perspectives

Jia,

Shen

2024

Cell Biosci

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Crohn’s disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.

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Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients

Li,

Han,

Zhao

et al. 2024

Medicine

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Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study – ERAP2, MET, CXCL9, and AGT – are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

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ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer

Cited by 4 publications

References 40 publications

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

Transcriptome-wide association studies associated with Crohn’s disease: challenges and perspectives

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients

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