Integrative Analysis of PAIP2B to Identify a Novel Biomarker for Pancreatic Ductal Adenocarcinoma
Yaoxian Xiang, Li Wang, Yurong Cheng, Huanjuan An, Chan Zhang, Jing Wang, Yingying Tong, Dong Yan
Integrative Analysis of PAIP2B to Identify a Novel Biomarker for Pancreatic Ductal Adenocarcinoma
The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B (PAIP2B) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of PAIP2B in pancreatic cancer samples, and validated the expression of PAIP2B in tumor tissue, using bioinformatics technology to explore the prognostic value of PAIP2B and its possible biological function. A significantly lower level of PAIP2B was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. PAIP2B reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of PAIP2B had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in PAIP2B expression. In addition, PAIP2B expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that PAIP2B regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of PAIP2B as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of PAIP2B in pancreatic cancer.
pancreatic carcinoma / PAIP2B / overall survival / prognosis / biomarker
[1] |
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73(01) 17-48
|
[2] |
Jethwa KR, Sannapaneni S, Mullikin TC. et al. Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer. J Gastrointest Oncol 2020; 11(06) 1408-1420
|
[3] |
Grossberg AJ, Chu LC, Deig CR. et al. Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma. CA Cancer J Clin 2020; 70(05) 375-403
|
[4] |
Tang H, Wei P, Chang P. et al. Genetic polymorphisms associated with pancreatic cancer survival: a genome-wide association study. Int J Cancer 2017; 141(04) 678-686
|
[5] |
Ivanov A, Shuvalova E, Egorova T. et al. Polyadenylate-binding protein-interacting proteins PAIP1 and PAIP2 affect translation termination. J Biol Chem 2019; 294(21) 8630-8639
|
[6] |
Khaleghpour K, Kahvejian A, De Crescenzo G. et al. Dual interactions of the translational repressor Paip2 with poly(A) binding protein. Mol Cell Biol 2001; 21(15) 5200-5213
|
[7] |
Mukherjee M, Goswami S. Identification of key deregulated RNA-binding proteins in pancreatic cancer by meta-analysis and prediction of their role as modulators of oncogenesis. Front Cell Dev Biol 2021; 9: 713852
|
[8] |
Ritchie ME, Phipson B, Wu D. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43(07) e47
|
[9] |
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012; 16(05) 284-287
|
[10] |
Szklarczyk D, Gable AL, Lyon D. et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47(D1): D607-D613
|
[11] |
Shannon P, Markiel A, Ozier O. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11) 2498-2504
|
[12] |
Newman AM, Liu CL, Green MR. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 2015; 12(05) 453-457
|
[13] |
Maeser D, Gruener RF, Huang RS. oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data. Brief Bioinform 2021; 22 (06) bbab260
|
[14] |
Gao Y, Shang S, Guo S. et al. Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data. Nucleic Acids Res 2021; 49(D1): D1251-D1258
|
[15] |
Kolbeinsson HM, Chandana S, Wright GP, Chung M. pancreatic cancer: a review of current treatment and novel therapies. J Invest Surg 2023; 36(01) 2129884
|
[16] |
Bailey P, Chang DK, Nones K. et al; Australian Pancreatic Cancer Genome Initiative. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016; 531(7592) 47-52
|
[17] |
Dreyer SB, Upstill-Goddard R, Legrini A. et al; Glasgow Precision Oncology Laboratory, Australian Pancreatic Genome Initiative. Genomic and molecular analyses identify molecular subtypes of pancreatic cancer recurrence. Gastroenterology2022; 162 (01) 320-324.e4
|
[18] |
Wang C, Jiang X, Qi J, Xu J, Yang G, Mi C. PAIP2 is a potential diagnostic and prognostic biomarker of breast cancer and is associated with immune infiltration. Front Genet 2022; 13: 1009056
|
[19] |
Berlanga JJ, Baass A, Sonenberg N. Regulation of poly(A) binding protein function in translation: characterization of the Paip2 homolog, Paip2B. RNA 2006; 12(08) 1556-1568
|
[20] |
Derry MC, Yanagiya A, Martineau Y, Sonenberg N. Regulation of poly(A)-binding protein through PABP-interacting proteins. Cold Spring Harb Symp Quant Biol 2006; 71: 537-543
|
[21] |
Onesto C, Berra E, Grépin R, Pagès G. Poly(A)-binding protein-interacting protein 2, a strong regulator of vascular endothelial growth factor mRNA. J Biol Chem 2004; 279(33) 34217-34226
|
[22] |
Ezzeddine N, Chang TC, Zhu W. et al. Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation. Mol Cell Biol 2007; 27(22) 7791-7801
|
[23] |
Rouillard AD, Gundersen GW, Fernandez NF. et al.The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database (Oxford) 2016; 2016: baw100
|
[24] |
Kenney C, Kunst T, Webb S. et al. Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma. Invest New Drugs 2021; 39(03) 821-828
|
[25] |
Yoshikawa T, Wu J, Otsuka M. et al. ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression. Nucleic Acids Res 2015; 43(15) 7577-7589
|
[26] |
Fukao A, Aoyama T, Fujiwara T. The molecular mechanism of translational control via the communication between the microRNA pathway and RNA-binding proteins. RNA Biol 2015; 12(09) 922-926
|
/
〈 | 〉 |