Differences in the Expression Patterns of Isoforms and Associated Genes in Astrocytic Brain Tumors

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Apr 23

PMID 35454784

Authors

Natalia Kurowska

Barbara Strzalka-Mrozik

Marcel Madej

Klaudia Pajak

Celina Kruszniewska-Rajs

Wojciech Kaspera

Joanna Magdalena Gola

Affiliations

Soon will be listed here.

Abstract

Genes associated with the TGFβ isoforms are involved in a number of different cancers, and their effect on the progression of brain tumors is also being discussed. Using an oligonucleotide microarray method, we assessed differences in expression patterns of genes in astrocytic brain tumor sections from 43 patients at different stages of disease. Quantitative mRNA assessment of the three TGFβ isoforms was also performed by real-time RT-qPCR. Oligonucleotide microarray data were analyzed using the PL-Grid Infrastructure. The microarray analysis showed a statistically significant (p < 0.05) increase in TGFβ1 and TGFβ2 expression in G3/G4 stage relative to G2, whereas real-time RT-qPCR validation confirmed this change only for the TGFβ2 isoform (p < 0.05). The oligonucleotide microarray method allowed the identification of 16 differential genes associated with TGFβ isoforms. Analysis of the STRING database showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001), and a significant number of proteins are involved in carcinogenesis. Differences in expression patterns of transcripts associated with TGFβ isoforms confirm that they play a role in astrocytic brain tumor transformation. Quantitative assessment of TGFβ2 mRNA may be a valuable method to complement the diagnostic process in the future.

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References

Huynh L, Hipolito C, Ten Dijke P . A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment. Biomolecules. 2019; 9(11). PMC: 6921009. DOI: 10.3390/biom9110743. View

Chen Q, Fu W, Tang X, Wang L, Niu Q, Wang S . ADP-Ribosylation Factor Like GTPase 4C (ARL4C) augments stem-like traits of glioblastoma cells by upregulating ALDH1A3. J Cancer. 2021; 12(3):818-826. PMC: 7778538. DOI: 10.7150/jca.45052. View

Chen C, Zhao K, Masci P, Lakhani S, Antonsson A, Simpson P . TGFβ isoforms and receptors mRNA expression in breast tumours: prognostic value and clinical implications. BMC Cancer. 2015; 15:1010. PMC: 4690401. DOI: 10.1186/s12885-015-1993-3. View

Hanif F, Muzaffar K, Perveen K, Malhi S, Simjee S . Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pac J Cancer Prev. 2017; 18(1):3-9. PMC: 5563115. DOI: 10.22034/APJCP.2017.18.1.3. View

Marko N, Toms S, Barnett G, Weil R . Genomic expression patterns distinguish long-term from short-term glioblastoma survivors: a preliminary feasibility study. Genomics. 2008; 91(5):395-406. DOI: 10.1016/j.ygeno.2008.01.002. View

Javle M, Li Y, Tan D, Dong X, Chang P, Kar S . Biomarkers of TGF-β signaling pathway and prognosis of pancreatic cancer. PLoS One. 2014; 9(1):e85942. PMC: 3896410. DOI: 10.1371/journal.pone.0085942. View

Molinaro A, Taylor J, Wiencke J, Wrensch M . Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol. 2019; 15(7):405-417. PMC: 7286557. DOI: 10.1038/s41582-019-0220-2. View

Liu Y, Song C, Shen F, Zhang J, Song S . IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma. PLoS One. 2019; 14(9):e0222999. PMC: 6764691. DOI: 10.1371/journal.pone.0222999. View

Miyazono K, Katsuno Y, Koinuma D, Ehata S, Morikawa M . Intracellular and extracellular TGF-β signaling in cancer: some recent topics. Front Med. 2018; 12(4):387-411. DOI: 10.1007/s11684-018-0646-8. View

10.

Meulmeester E, Ten Dijke P . The dynamic roles of TGF-β in cancer. J Pathol. 2010; 223(2):205-18. DOI: 10.1002/path.2785. View

11.

Urbanaviciute R, Zabitaite R, Krisciukaitis A, Deltuva V, Skiriute D . Serum protein triplet TGF-β1, TIMP-1, and YKL-40 serve as diagnostic and prognostic profile for astrocytoma. Sci Rep. 2021; 11(1):13100. PMC: 8222249. DOI: 10.1038/s41598-021-92328-3. View

12.

Soomro S, Ting L, Qing Y, Ren M . Molecular biology of glioblastoma: Classification and mutational locations. J Pak Med Assoc. 2017; 67(9):1410-1414. View

13.

Wang H, Wang X, Xu L, Zhang J, Cao H . Prognostic significance of age related genes in patients with lower grade glioma. J Cancer. 2020; 11(13):3986-3999. PMC: 7171497. DOI: 10.7150/jca.41123. View

14.

Reifenberger G, Wirsching H, Knobbe-Thomsen C, Weller M . Advances in the molecular genetics of gliomas - implications for classification and therapy. Nat Rev Clin Oncol. 2016; 14(7):434-452. DOI: 10.1038/nrclinonc.2016.204. View

15.

Luo D, Chen W, Tian Y, Li J, Xu X, Chen C . Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is overexpressed in glioma and associated with poor prognosis in glioma patients. Onco Targets Ther. 2017; 10:2173-2181. PMC: 5403010. DOI: 10.2147/OTT.S133022. View

16.

Ruano Y, Mollejo M, Camacho F, de Lope A, Fiano C, Ribalta T . Identification of survival-related genes of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma multiforme. Cancer. 2008; 112(7):1575-84. DOI: 10.1002/cncr.23338. View

17.

Principe D, Doll J, Bauer J, Jung B, Munshi H, Bartholin L . TGF-β: duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst. 2014; 106(2):djt369. PMC: 3952197. DOI: 10.1093/jnci/djt369. View

18.

Tyburczy M, Kotulska K, Pokarowski P, Mieczkowski J, Kucharska J, Grajkowska W . Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications. Am J Pathol. 2010; 176(4):1878-90. PMC: 2843477. DOI: 10.2353/ajpath.2010.090950. View

19.

Preukschas M, Hagel C, Schulte A, Weber K, Lamszus K, Sievert H . Expression of eukaryotic initiation factor 5A and hypusine forming enzymes in glioblastoma patient samples: implications for new targeted therapies. PLoS One. 2012; 7(8):e43468. PMC: 3424167. DOI: 10.1371/journal.pone.0043468. View

20.

Yang L, Liu M, Deng C, Gu Z, Gao Y . Expression of transforming growth factor-β1 (TGF-β1) and E-cadherin in glioma. Tumour Biol. 2012; 33(5):1477-84. DOI: 10.1007/s13277-012-0398-z. View