Integrated Analysis of DNA Methylation and MRNA Expression Profiles to Identify Key Genes Involved in the Regrowth of Clinically Non-functioning Pituitary Adenoma

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Feb 5

PMID 32015217

Citations 11

Authors

Sen Cheng

Chuzhong Li

Weiyan Xie

Yazhou Miao

Jing Guo

Jichao Wang

Yazhuo Zhang

Affiliations

Soon will be listed here.

Abstract

Tumour regrowth is a key characteristic of clinically non-functioning pituitary adenoma (NFPA). No applicable prognosis evaluation method is available for post-operative patients. We aimed to identify DNA methylation biomarkers that can facilitate prognosis evaluation. Genome-wide DNA methylation and mRNA microarray analyses were performed for tumour samples from 71 NFPA patients. Differentially expressed genes and methylated genes were identified based on the regrowth vs non-regrowth grouping. There were 139 genes that showed alterations in methylation status and expression level, and only 13 genes showed a negative correlation. The progression-free analysis found that are related to tumour regrowth. A prognosis-prediction model was built based on all 13 genes from integrated analysis, and the 6-gene model achieved the best area under the receiver operating characteristic curves (AUC) of 0.820, compared with 0.785 and 0.568 for the 13-gene and 7-gene models, respectively. Our prognostic biomarkers were validated by pyrosequencing and RT-PCR. and was found to be independent prognostic factors of tumour regrowth with univariate Cox regression. The DNA methylation and expression levels of and are associated with tumour regrowth, and may serve as biomarkers for predicting the prognosis of patients with NFPA.

Citing Articles

DNA Methylation in Pituitary Adenomas: A Scoping Review.

Moller M, Nortvig M, Andersen M, Poulsen F Int J Mol Sci. 2025; 26(2).

PMID: 39859246 PMC: 11765255. DOI: 10.3390/ijms26020531.

Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

Moller M, Andersen M, Halle B, Pedersen C, Boldt H, Tan Q Cancers (Basel). 2024; 16(12).

PMID: 38927917 PMC: 11201450. DOI: 10.3390/cancers16122210.

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer.

Zhang W, Chen X, Wei Y, Wang X, Chen X, Chi B Eur J Med Res. 2024; 29(1):257.

PMID: 38689322 PMC: 11059691. DOI: 10.1186/s40001-024-01844-1.

Characterization and comparison of insulinoma tumor model and pancreatic damage caused by the tumor, and identification of possible markers.

Karatug Kacar A, Bulutay P, Aylar D, Celikten M, Bolkent S Mol Biol Rep. 2024; 51(1):109.

PMID: 38227104 DOI: 10.1007/s11033-023-08942-z.

Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors.

Whyte E, Nezu M, Chik C, Tateno T Endocrinol Metab (Seoul). 2023; 38(6):631-654.

PMID: 37964483 PMC: 10764990. DOI: 10.3803/EnM.2023.1838.

References

Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G . TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 1996; 15(5):1004-11. PMC: 449995. View

Gruppetta M, Formosa R, Falzon S, Ariff Scicluna S, Falzon E, Degeatano J . Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas. Pituitary. 2017; 20(3):358-371. DOI: 10.1007/s11102-017-0803-0. View

Walzak A, Veldhoen N, Feng X, Riabowol K, Helbing C . Expression profiles of mRNA transcript variants encoding the human inhibitor of growth tumor suppressor gene family in normal and neoplastic tissues. Exp Cell Res. 2007; 314(2):273-85. DOI: 10.1016/j.yexcr.2007.07.029. View

Simpson D, Bicknell J, McNicol A, Clayton R, Farrell W . Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer. 1999; 24(4):328-36. View

Wallace J, Li F, Balakrishnan S, Cantemir-Stone C, Pecot T, Martin C . Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer. PLoS One. 2013; 8(8):e71533. PMC: 3745457. DOI: 10.1371/journal.pone.0071533. View

Lesage F, Lauritzen I, Duprat F, Reyes R, Fink M, Heurteaux C . The structure, function and distribution of the mouse TWIK-1 K+ channel. FEBS Lett. 1997; 402(1):28-32. DOI: 10.1016/s0014-5793(96)01491-3. View

Kumamoto K, Fujita K, Kurotani R, Saito M, Unoki M, Hagiwara N . ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. Int J Cancer. 2009; 125(6):1306-15. PMC: 2790157. DOI: 10.1002/ijc.24437. View

Ostrom Q, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C . CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol. 2017; 19(suppl_5):v1-v88. PMC: 5693142. DOI: 10.1093/neuonc/nox158. View

Cury M, Fernandes J, Machado H, Elias L, Moreira A, de Castro M . Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging assessment, therapeutic management and outcome. Arq Bras Endocrinol Metabol. 2009; 53(1):31-9. DOI: 10.1590/s0004-27302009000100006. View

10.

Kou Y, Koag M, Lee S . Structural and Kinetic Studies of the Effect of Guanine N7 Alkylation and Metal Cofactors on DNA Replication. Biochemistry. 2018; 57(34):5105-5116. PMC: 6113087. DOI: 10.1021/acs.biochem.8b00331. View

11.

Bosch N, Caceres M, Cardone M, Carreras A, Ballana E, Rocchi M . Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events. Hum Mol Genet. 2007; 16(21):2572-82. DOI: 10.1093/hmg/ddm209. View

12.

Noh T, Jeong H, Lee M, Kim T, Kim S, Lee E . Predicting recurrence of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2009; 94(11):4406-13. DOI: 10.1210/jc.2009-0471. View

13.

Day R, Liu J, Sundmark V, Kawecki M, Berry D, Elsholtz H . Selective inhibition of prolactin gene transcription by the ETS-2 repressor factor. J Biol Chem. 1998; 273(48):31909-15. DOI: 10.1074/jbc.273.48.31909. View

14.

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

15.

Roelfsema F, Biermasz N, Pereira A . Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary. 2011; 15(1):71-83. PMC: 3296023. DOI: 10.1007/s11102-011-0347-7. View

16.

Kou Y, Koag M, Lee S . N7 methylation alters hydrogen-bonding patterns of guanine in duplex DNA. J Am Chem Soc. 2015; 137(44):14067-70. PMC: 5704973. DOI: 10.1021/jacs.5b10172. View

17.

Ythier D, Brambilla E, Binet R, Nissou D, Vesin A, De Fraipont F . Expression of candidate tumor suppressor gene ING2 is lost in non-small cell lung carcinoma. Lung Cancer. 2009; 69(2):180-6. DOI: 10.1016/j.lungcan.2009.11.006. View

18.

Kober P, Boresowicz J, Rusetska N, Maksymowicz M, Goryca K, Kunicki J . DNA methylation profiling in nonfunctioning pituitary adenomas. Mol Cell Endocrinol. 2018; 473:194-204. DOI: 10.1016/j.mce.2018.01.020. View

19.

Snyder P, Bashey H, Phillips J, Gennarelli T . Comparison of hormonal secretory behavior of gonadotroph cell adenomas in vivo and in culture. J Clin Endocrinol Metab. 1985; 61(6):1061-5. DOI: 10.1210/jcem-61-6-1061. View

20.

Wang Z, Thiruvengadam S, Cheng Y, Ma K, Simsek C, Tieu A . Methylation Biomarker Panel Performance in EsophaCap Cytology Samples for Diagnosing Barrett's Esophagus: A Prospective Validation Study. Clin Cancer Res. 2019; 25(7):2127-2135. PMC: 6594757. DOI: 10.1158/1078-0432.CCR-18-3696. View