Identification of As a Potential Core Gene Involved in the Metastasis of Clear Cell Renal Cell Carcinoma

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Aug 9

PMID 32765073

Citations 4

Authors

Yi Sun

Junxia Zou

Wei Ouyang

Ke Chen

Affiliations

Soon will be listed here.

Abstract

Background: Metastasis is the main cause of treatment failure in various cancer, including ccRCC. However, the key genes involved in ccRCC metastasis remain largely unknown.

Purpose: The identification of the aberrant gene expression patterns associated with metastatic traits is of great clinical significance. The aim of this study was to investigate the clinical significance and function of PDE7B in ccRCC.

Materials And Methods: Expression profiling data for patient-matched primary and metastatic ccRCC tumors were obtained from GEO Dataset. Limma package was used to identify differentially expressed genes (DEGs) between the metastatic and the primary groups. Gene Ontology, Kyoto Encyclopedia of Genes Genomes (KEGG), and PPI network analysis were used to study the interacting activities and the interconnection of the DEGs. CCK-8 assays and Transwell assays were performed to detect the proliferation and migration of renal cancer cells.

Results: We obtained 163 DEGs, including 132 that were upregulated and 31 that were downregulated in metastatic ccRCC tissues. Both Gene Ontology function and KEGG pathway analysis showed that DEGs were involved in extracellular matrix (ECM) organization and cell adhesion. After utilizing PPI network to explore the interconnection among the DEGs, 22 genes were selected as the hub genes. Subsequently, survival analysis revealed that seven hub genes (SFN, NKX2-1, HP, MAPT, EPHA4, KCNAB1, and PDE7B) were significantly associated with overall survival disease-specific survival, and progression-free interval in ccRCC. Moreover, the low expression of PDE7B was found in clinical ccRCC samples and correlated with TNM stage and histologic grade. We further showed that knockdown of PDE7B increased cell growth and migration of renal cancer cells.

Conclusion: Our results implicated that PDE7B may play a key role in the development of metastatic RCC.

Citing Articles

The Effects of miR-22-3p on Differentiation of Human Dental Pulp Stem Cells into Neural Progenitor-Like Cells.

Gul M, Khattak M, Qaisar R, Jayakumar M, Samsudin A, Khan A Mol Neurobiol. 2025; .

PMID: 39900772 DOI: 10.1007/s12035-025-04702-1.

Methylation-regulated tumor suppressor gene PDE7B promotes HCC invasion and metastasis through the PI3K/AKT signaling pathway.

Du Y, Xu Y, Guo X, Tan C, Zhu X, Liu G BMC Cancer. 2024; 24(1):624.

PMID: 38778317 PMC: 11112795. DOI: 10.1186/s12885-024-12364-w.

HAGLR, A Long Non-coding RNA of Potential Tumor Suppressive Function in Clear Cell Renal Cell Carcinoma: Diagnostic and Prognostic Implications.

Bardhan A, Banerjee A, Pal D, Ghosh A Mol Biotechnol. 2023; 66(12):3485-3497.

PMID: 37955777 DOI: 10.1007/s12033-023-00948-z.

Integrative Bioinformatics Analysis Demonstrates the Prognostic Value of Chromatin Accessibility Biomarkers in Clear Cell Renal Cell Carcinoma.

Meng M, Lan T, Tian D, Qin Z, Li Y, Li J Front Oncol. 2022; 11:814396.

PMID: 34993155 PMC: 8724435. DOI: 10.3389/fonc.2021.814396.

Identification of adhesion-associated extracellular matrix component thrombospondin 3 as a prognostic signature for clear cell renal cell carcinoma.

Chen X, Lin J, Chen M, Chen Q, Cai Z, Tang A Investig Clin Urol. 2022; 63(1):107-117.

PMID: 34983129 PMC: 8756151. DOI: 10.4111/icu.20210273.

References

Lalani A, Gray K, Albiges L, Callea M, Pignon J, Pal S . Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression. Oncotarget. 2017; 8(61):103428-103436. PMC: 5732739. DOI: 10.18632/oncotarget.21952. View

Cao L, Zhang W, Liu X, Yang P, Wang J, Hu K . The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia. Sci Rep. 2019; 9(1):16991. PMC: 6861270. DOI: 10.1038/s41598-019-53563-x. View

Vitale G, Dicitore A, Mari D, Cavagnini F . A new therapeutic strategy against cancer: cAMP elevating drugs and leptin. Cancer Biol Ther. 2009; 8(12):1191-3. DOI: 10.4161/cbt.8.12.8937. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Linehan W, Ricketts C . The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications. Nat Rev Urol. 2019; 16(9):539-552. DOI: 10.1038/s41585-019-0211-5. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Zimmerman N, Roy I, Hauser A, Wilson J, Williams C, Dwinell M . Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells. Mol Carcinog. 2013; 54(3):203-15. PMC: 4087083. DOI: 10.1002/mc.22091. View

Zhang L, Murray F, Rassenti L, Pu M, Kelly C, Kanter J . Cyclic nucleotide phosphodiesterase 7B mRNA: an unfavorable characteristic in chronic lymphocytic leukemia. Int J Cancer. 2010; 129(5):1162-9. PMC: 3111850. DOI: 10.1002/ijc.25785. View

Zou T, Liu J, She L, Chen J, Zhu T, Yin J . A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer. J Cancer. 2019; 10(27):6848-6857. PMC: 6909948. DOI: 10.7150/jca.36614. View

10.

Reimand J, Isserlin R, Voisin V, Kucera M, Tannus-Lopes C, Rostamianfar A . Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap. Nat Protoc. 2019; 14(2):482-517. PMC: 6607905. DOI: 10.1038/s41596-018-0103-9. View

11.

Lowery F, Yu D . Growth factor signaling in metastasis: current understanding and future opportunities. Cancer Metastasis Rev. 2012; 31(3-4):479-91. DOI: 10.1007/s10555-012-9380-x. View

12.

Yao X, Tan J, JunLiang Lim K, Koh J, Ooi W, Li Z . Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma. Cancer Discov. 2017; 7(11):1284-1305. DOI: 10.1158/2159-8290.CD-17-0375. View

13.

Zhou G, Soufan O, Ewald J, Hancock R, Basu N, Xia J . NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019; 47(W1):W234-W241. PMC: 6602507. DOI: 10.1093/nar/gkz240. View

14.

Brooks M, Jackson E, Warrington N, Luo J, Forys J, Taylor S . PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells. PLoS One. 2014; 9(9):e107397. PMC: 4159344. DOI: 10.1371/journal.pone.0107397. View

15.

Ho T, Serie D, Parasramka M, Cheville J, Bot B, Tan W . Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes. Ann Oncol. 2016; 28(3):604-610. PMC: 5834119. DOI: 10.1093/annonc/mdw652. View

16.

Fu Q, Xu L, Wang Y, Jiang Q, Liu Z, Zhang J . Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion. Eur Urol. 2018; 75(5):752-763. DOI: 10.1016/j.eururo.2018.09.030. View

17.

Zhang L, Murray F, Zahno A, Kanter J, Chou D, Suda R . Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2008; 105(49):19532-7. PMC: 2614795. DOI: 10.1073/pnas.0806152105. View

18.

Lambert A, Pattabiraman D, Weinberg R . Emerging Biological Principles of Metastasis. Cell. 2017; 168(4):670-691. PMC: 5308465. DOI: 10.1016/j.cell.2016.11.037. View

19.

Chen K, Xiao H, Zeng J, Yu G, Zhou H, Huang C . Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer. Clin Cancer Res. 2016; 23(13):3428-3441. PMC: 5440213. DOI: 10.1158/1078-0432.CCR-16-2020. View

20.

Nam H, Chandrashekar D, Kundu A, Shelar S, Kho E, Sonpavde G . Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis. Mol Cancer Res. 2018; 17(1):84-96. PMC: 7222224. DOI: 10.1158/1541-7786.MCR-17-0636. View