Expression and Prognostic Analyses of the Insulin-like Growth Factor 2 mRNA Binding Protein Family in Human Pancreatic Cancer

Chen, Xiaoping; Hu, Shu-Yi; Qin, Xihu; Zhu, Chunfu

doi:10.21203/rs.3.rs-58042/v2

Cited by 2 publications

(3 citation statements)

References 19 publications

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“…The presently detected missense mutations in the gene may cause dysregulation of its tumor suppressor activity, thereby promoting the development of PDAC. Likewise, increased expression of IGF2BP3 (insulin‐like growth factor 2 mRNA‐binding protein 3) was found to promote invasiveness and metastasis of PDAC, 42,43 while dysregulation of SGK2 (serum/glucocorticoid regulated kinase 2) affected treatment response in PDAC 44 . The RIF1 gene has emerged as a conserved regulator of chromosome maintenance, acting to control DNA replication and repair.…”

Section: Discussionmentioning

confidence: 99%

“…(insulin-like growth factor 2 mRNA-binding protein 3) was found to promote invasiveness and metastasis of PDAC, 42,43 while dysregulation of SGK2 (serum/glucocorticoid regulated kinase 2) affected treatment response in PDAC. 44 The RIF1 gene has emerged as a conserved regulator of chromosome maintenance, acting to control DNA replication and repair.…”

Section: The Relevance Of Significant Genes By Association Testmentioning

confidence: 99%

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Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients

et al. 2021

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First-degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk-assessment and management of high-risk individuals. Using a Danish cohort of 27 FPC families, we performed whole-genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer-related genes and cancer-driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes were enriched by gene clusters encoding for extracellular matrix and associated proteins. PTV genes were overrepresented by functions related to transport of small molecules, innate immune system, ion channel transport, and stimuli-sensing channels. In conclusion, FDRs of FPC patients carry rare germline variants related to cancer pathogenesis that may contribute to increased susceptibility to PDAC. The identified variants may potentially be useful for risk prediction of high-risk individuals in predisposed families.

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Section: Discussionmentioning

confidence: 99%

Section: The Relevance Of Significant Genes By Association Testmentioning

confidence: 99%

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients

et al. 2021

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“…High expression of IGF2BP2 accelerates pancreatic cancer cell proliferation through regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway (37). IGF2BP2 and IGF2BP3 are significantly increased in pancreatic cancer cells, and the inhibition of IGF2BP2 and IGF2BP3 can significantly reduce pancreatic cancer cell invasion (38). IGF2BP3 affects malignancy-related RNA regulation through modulating miRNA-mRNA interactions in PDAC (39).…”

Section: Discussionmentioning

confidence: 99%

The expression of m6A regulators correlated with the immune microenvironment plays an important role in the prognosis of pancreatic ductal adenocarcinoma

Yao¹,

Luo²,

Xiang³

et al. 2022

Gland Surg

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Background: The relationship between N6-methyladenosine (m 6 A) RNA methylation regulators and the tumor immune microenvironment has been extensively studied. Nevertheless, the potential function of m 6 A regulators in the tumor immune landscape of pancreatic ductal adenocarcinoma (PDAC) remains to be fully elucidated.Methods: Here, we systematically evaluated the expression of 19 m 6 A regulators in PDAC patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Utilizing consensus clustering, the PDAC patients were segmented into two subgroups according to the expression of 19 m 6 A regulators. A prognostic risk signature of 5 m 6 A methylation regulators (ALKBH5, IGF2BP2, IGF2BP3, LRPPRC, and KIAA1429) was then built, and the PDAC patients were divided into high-risk and low-risk groups. Subsequently, differences in independent prognostic parameters, risk score distribution, survival, and cluster analysis between high-risk and low-risk groups were analyzed.Results: We found two subgroups with dramatically different immune landscapes and prognoses. Subsequently, differences in independent prognostic parameters, risk score distribution, survival, and cluster analysis between the high-risk and low-risk groups were found. Moreover, these gene signatures displayed good discriminative performances in the GEO datasets. We also found that the risk score was positively correlated with the tumor mutation burden (TMB), and the TMB value was higher in the high-risk scoring group. The low-risk scoring group was linked by a stronger response to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy and clinical advantages in the immunotherapeutic advanced urothelial cancer (IMvigor210) cohort. Ultimately, we found that these 5 m 6 A regulators had a fatal regulatory role on the tumor immune microenvironment in PDAC patients. Conclusions:The construction signature based on the m 6 A regulators may be crucial regulators of the tumor immune microenvironment in PDAC, providing a new approach to improving the immunotherapy strategy for PDAC patients.

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Expression and Prognostic Analyses of the Insulin-like Growth Factor 2 mRNA Binding Protein Family in Human Pancreatic Cancer

Cited by 2 publications

References 19 publications

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients

The expression of m6A regulators correlated with the immune microenvironment plays an important role in the prognosis of pancreatic ductal adenocarcinoma

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