Identification of Hub Genes and Their Novel Diagnostic and Prognostic Significance in Pancreatic Adenocarcinoma

Overview

Journal Cancer Biol Med

Specialty Oncology

Date 2021 Aug 17

PMID 34403221

Citations 5

Authors

Duo Zuo

Yongzi Chen

Xinwei Zhang

Zhuozhi Wang

Wenna Jiang

Fan Tang

Runfen Cheng

Yi Sun

Lu Sun

Li Ren

Rui Liu

Affiliations

Soon will be listed here.

Abstract

Objective: The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed.

Methods: Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID. Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER. Cox proportional hazard regression analyses were also performed. Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs.

Results: We identified 59 hub genes among 752 DEGs. GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway. We also discovered that and were associated with immune cell infiltration in the PA microenvironment. Additionally, mRNA might be used as an independent risk factor for the prognoses of PA patients. Furthermore, the protein encoded by , which exists in peripheral blood, was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls (area under the curve: 0.902, 95% confidence interval: 0.819-0.961).

Conclusions: Our study suggested that and were associated with immune cell infiltration in the PA microenvironment, while mRNA expression might be an independent risk factor for the survival prognoses of PA patients. Moreover, ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.

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References

Shen J, Yu S, Sun X, Yin M, Fei J, Zhou J . Identification of key biomarkers associated with development and prognosis in patients with ovarian carcinoma: evidence from bioinformatic analysis. J Ovarian Res. 2019; 12(1):110. PMC: 6857166. DOI: 10.1186/s13048-019-0578-1. View

Andtbacka R, Kaufman H, Collichio F, Amatruda T, Senzer N, Chesney J . Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015; 33(25):2780-8. DOI: 10.1200/JCO.2014.58.3377. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Kumar R, Patiyal S, Kumar V, Nagpal G, Raghava G . In Silico Analysis of Gene Expression Change Associated with Copy Number of Enhancers in Pancreatic Adenocarcinoma. Int J Mol Sci. 2019; 20(14). PMC: 6679006. DOI: 10.3390/ijms20143582. View

Liu P, Weng Y, Sui Z, Wu Y, Meng X, Wu M . Quantitative secretomic analysis of pancreatic cancer cells in serum-containing conditioned medium. Sci Rep. 2016; 6:37606. PMC: 5116583. DOI: 10.1038/srep37606. View

Zhao X, Wang X, Fang L, Lan C, Zheng X, Wang Y . A combinatorial strategy using YAP and pan-RAF inhibitors for treating KRAS-mutant pancreatic cancer. Cancer Lett. 2017; 402:61-70. DOI: 10.1016/j.canlet.2017.05.015. View

Badea L, Herlea V, Dima S, Dumitrascu T, Popescu I . Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology. 2009; 55(88):2016-27. View

Barrett T, Troup D, Wilhite S, Ledoux P, Rudnev D, Evangelista C . NCBI GEO: mining tens of millions of expression profiles--database and tools update. Nucleic Acids Res. 2006; 35(Database issue):D760-5. PMC: 1669752. DOI: 10.1093/nar/gkl887. View

Zhang X, Pan Y, Fu H, Zhang J . Nucleolar and Spindle Associated Protein 1 (NUSAP1) Inhibits Cell Proliferation and Enhances Susceptibility to Epirubicin In Invasive Breast Cancer Cells by Regulating Cyclin D Kinase (CDK1) and DLGAP5 Expression. Med Sci Monit. 2018; 24:8553-8564. PMC: 6278864. DOI: 10.12659/MSM.910364. View

10.

Iacobuzio-Donahue C, Maitra A, Olsen M, Lowe A, Van Heek N, Rosty C . Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol. 2003; 162(4):1151-62. PMC: 1851213. DOI: 10.1016/S0002-9440(10)63911-9. View

11.

Grutzmann R, Boriss H, Ammerpohl O, Luttges J, Kalthoff H, Schackert H . Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes. Oncogene. 2005; 24(32):5079-88. DOI: 10.1038/sj.onc.1208696. View

12.

Kurokawa C, Iankov I, Galanis E . A key anti-viral protein, RSAD2/VIPERIN, restricts the release of measles virus from infected cells. Virus Res. 2019; 263:145-150. PMC: 6615567. DOI: 10.1016/j.virusres.2019.01.014. View

13.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

14.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

15.

Branchi V, Garcia S, Radhakrishnan P, Gyorffy B, Hissa B, Schneider M . Prognostic value of DLGAP5 in colorectal cancer. Int J Colorectal Dis. 2019; 34(8):1455-1465. DOI: 10.1007/s00384-019-03339-6. View

16.

Zuckerman D, Ryan D . Adjuvant therapy for pancreatic cancer: a review. Cancer. 2007; 112(2):243-9. DOI: 10.1002/cncr.23174. View

17.

Neesse A, Bauer C, Ohlund D, Lauth M, Buchholz M, Michl P . Stromal biology and therapy in pancreatic cancer: ready for clinical translation?. Gut. 2018; 68(1):159-171. DOI: 10.1136/gutjnl-2018-316451. View

18.

Yu L, Chen S, Bao H, Zhang W, Liao M, Liang Q . The role of lncRNA CASC2 on prognosis of malignant tumors: a meta-analysis and bioinformatics. Onco Targets Ther. 2018; 11:4355-4365. PMC: 6065597. DOI: 10.2147/OTT.S166132. View

19.

Grutzmann R, Pilarsky C, Ammerpohl O, Luttges J, Bohme A, Sipos B . Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia. 2004; 6(5):611-22. PMC: 1531666. DOI: 10.1593/neo.04295. View

20.

Fukuhisa H, Seki N, Idichi T, Kurahara H, Yamada Y, Toda H . Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8. J Hum Genet. 2019; 64(6):521-534. DOI: 10.1038/s10038-019-0584-6. View