The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer

Heinzman, Zachary; Schmidt, Connor; Sliwinski, Marek K.; Goonesekere, Nalin C. W.

doi:10.3390/ph14030209

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…Using this approach and verifying the data using individual gene expression data, we found that AGR2, CEACAM6, GNMT, PDIA2, POSTN, RBPJL, and S100P are upregulated in pancreatic tumor tissue as compared to non-tumor tissue from Black and White patients (Fig 1). The protein products from AGR2 [16,[23][24][25], CEAMAN6 [26][27][28], GNMT [29,30], PDIA2 [31,32], POSTN [17,33,34], RBPJL [35,36] and S100P [37][38][39] have been reported as potential diagnostic and prognostic biomarkers for pancreatic cancer or have demonstrated to be involved in either pancreatic cancer, initiation, migration, invasion, metastasis, or chemoresistance. This report provides additional evidence to support that these genes are specifically upregulated in pancreatic tumor tissue as compared to non-tumor tissue and their products could potentially serve as differentiating biomarkers in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

et al. 2023

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In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black (n = 8) and White (n = 20) patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. To validate these results, the expression of four genes (AGR2, POSTN, TFF1, and CP) reported to be up-regulated in pancreatic tumor tissue as compared to non-tumor tissue were confirmed using quantitative PCR. Transcriptomic analysis that compared pancreatic tumor tissue from Black and White patients revealed differential expression in 1,200 genes, while a comparison of the non-tumor and tumor gene expression differences within each race revealed over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

et al. 2023

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“…[ 27 ] GNMT is significantly downregulated in most PC cell lines, and PGG upregulated GNMT expression in a dose-dependent manner, which could be a therapeutic target and biomarker for PC. [ 28 ] Jeong et al found that a 7B (Kelch) domain-containing Kelch structural domain 7B (KLHDC7 B) was highly methylated at the promoter but upregulated in BRCA and was significantly associated with gene regulatory activity in the interferon signaling pathway during breast carcinogenesis. [ 29 ] There are still no relevant studies on TUBA3E in BRCA and remains to be explored further.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of molecular subtypes and a 9-gene risk model for breast cancer

Feng

2023

Medicine

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The long-term efficacy of treatment, heterogeneity, and complexity in the tumor microenvironment remained a clinical challenge in breast cancer (BRCA). There is a need to classify and refine appropriate therapeutic intervention decisions. A stable subtype classification based on gene expression associated with neoadjuvant chemotherapy (NAC) prognosis and assessment on the clinical features, immune infiltration, and mutational characteristics of the different subcategories was performed using ConsensusClusterPlus. We constructed a prognostic model by the least absolute shrinkage and selection operator regression (LASSO) and univariate Cox regression method and further investigated the association between the risk model and clinical features, mutation and immune characteristics of BRCA. We constructed 3 molecular clusters associated with NAC. We found that cluster 1 had the best prognosis, while cluster 3 showed a poor prognosis. Cluster 3 were associated with the advance stage, higher mutation score, activated oncogenic, and lower tumor immune dysfunction and exclusion (TIDE) score. Subsequently, we constructed a prognosis-related risk model comprising 9 genes (RLN2, MSLN, SAPCD2, LY6D, CACNG4, TUBA3E, LAMP3, GNMT, KLHDC7B). The higher-risk group exhibited lower immune infiltration and demonstrated improved overall survival (OS) in both the independent validation cohort. Finally, by combining clinicopathological features with the NAC-related prognostic risk model, we enhanced the accuracy of survival prediction and model performance. Here, we revealed 3 new molecular subtypes based on prognosis-related genes for BRCA NAC and developed a prognostic risk model. It has the potential to aid in the selection of appropriate individualized treatment and the prediction of patient prognosis.

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The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer

Cited by 2 publications

References 32 publications

Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

Identification and validation of molecular subtypes and a 9-gene risk model for breast cancer

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