FGFR-2 and Epithelial-Mesenchymal Transition in Endometrial Cancer

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 Sep 23

PMID 36143062

Authors

Olga Adamczyk-Gruszka

Agata Horecka-Lewitowicz

Jakub Gruszka

Monika Wawszczak-Kasza

Agnieszka Strzelecka

Piotr Lewitowicz

Affiliations

Soon will be listed here.

Abstract

Background: At present, EC staging is based on the WHO conservative criteria, which only consider the percentage of gland formation. The molecular subgrouping of EC recently proposed by the Cancer Genome Atlas (TCGA) represents a milestone in precise molecular-based patient triage. The present study aimed to investigate the influence of FGFR-2 on the epithelial-mesenchymal transition (EMT) and whether it can lead to endometrial cancer dedifferentiation.

Methods: One hundred and three White female patients with confirmed EC were enrolled in our research. For the analysis, we performed next-generation sequencing and immunohistochemical analyses of E-cadherin, β-catenin, and vimentin.

Results: Tumor grade progression was closely correlated with LVI ( = 0.0338), expression of vimentin ( = 0.000), tumor budding ( = 0.000), and lack of E-cadherin ( = 0.0028). Similar observations were noted with regard to TNM/FIGO stage progression. In terms of FGFR-2 mutation, we found the following correlation -values: LVI ( = 0.069), expression of vimentin ( = 0.000), tumor budding ( = 0.000), and lack of E-cadherin ( = 0.000), RFS ( = 0.032), ECSS ( = 0.047).

Conclusions: FGFR-2 is the important factor influencing on EMT.

Citing Articles

Lower mRNA Expression and Higher Levels of in HER2-Positive Breast Cancer.

Dix-Peek T, Dickens C, Valcarcel J, Duarte R Biology (Basel). 2024; 13(11).

PMID: 39596875 PMC: 11591975. DOI: 10.3390/biology13110920.

Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool.

Rodrigues D, Reis R, Pirraco R J Biomed Sci. 2024; 31(1):13.

PMID: 38254117 PMC: 10804490. DOI: 10.1186/s12929-024-00997-9.

The impact of poor metabolic health on aggressive breast cancer: adipose tissue and tumor metabolism.

Sankofi B, Valencia-Rincon E, Sekhri M, Ponton-Almodovar A, Bernard J, Wellberg E Front Endocrinol (Lausanne). 2023; 14:1217875.

PMID: 37800138 PMC: 10548218. DOI: 10.3389/fendo.2023.1217875.

Independent Tissue-Based Biomarkers in Endometrioid Endometrial Cancer: Tumor Budding in Microsatellite Instability and WHO Grading in Copy-Number-Low Patients.

Stogbauer F, Gess B, Brambs C, Lautizi M, Kacprowski T, Ourailidis I Cancers (Basel). 2023; 15(15).

PMID: 37568650 PMC: 10416921. DOI: 10.3390/cancers15153832.

Immune Environment and Immunotherapy in Endometrial Carcinoma and Cervical Tumors.

Laine A, Gonzalez-Lopez A, Hasan U, Ohkuma R, Ray-Coquard I Cancers (Basel). 2023; 15(7).

PMID: 37046702 PMC: 10093320. DOI: 10.3390/cancers15072042.

References

Vermij L, Smit V, Nout R, Bosse T . Incorporation of molecular characteristics into endometrial cancer management. Histopathology. 2019; 76(1):52-63. PMC: 6972558. DOI: 10.1111/his.14015. View

Guasti L, Sze W, McKay T, Grose R, King P . FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development. Mol Cell Endocrinol. 2013; 371(1-2):182-8. PMC: 3650577. DOI: 10.1016/j.mce.2013.01.014. View

Haase M, Thiel A, Scholl U, Ashmawy H, Schott M, Ehlers M . Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma. BMC Res Notes. 2020; 13(1):282. PMC: 7288682. DOI: 10.1186/s13104-020-05110-5. View

Colas E, Pedrola N, Devis L, Ertekin T, Campoy I, Martinez E . The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol. 2012; 14(10):715-20. DOI: 10.1007/s12094-012-0866-3. View

Mayakonda A, Lin D, Assenov Y, Plass C, Koeffler H . Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018; 28(11):1747-1756. PMC: 6211645. DOI: 10.1101/gr.239244.118. View

Chioni A, Grose R . Biological Significance and Targeting of the FGFR Axis in Cancer. Cancers (Basel). 2021; 13(22). PMC: 8616401. DOI: 10.3390/cancers13225681. View

Oaknin A, Bosse T, Creutzberg C, Giornelli G, Harter P, Joly F . Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022; 33(9):860-877. DOI: 10.1016/j.annonc.2022.05.009. View

Oplawski M, Nowakowski R, Srednicka A, Ochnik D, Grabarek B, Boron D . Molecular Landscape of the Epithelial-Mesenchymal Transition in Endometrioid Endometrial Cancer. J Clin Med. 2021; 10(7). PMC: 8038735. DOI: 10.3390/jcm10071520. View

Li M, Xin X, Jin Z, Hua T, Wang H, Wang H . Transcriptomic analysis of stromal cells from patients with endometrial carcinoma. Int J Clin Exp Pathol. 2020; 10(9):9853-9857. PMC: 6965954. View

10.

Fatima I, Barman S, Rai R, Thiel K, Chandra V . Targeting Wnt Signaling in Endometrial Cancer. Cancers (Basel). 2021; 13(10). PMC: 8152465. DOI: 10.3390/cancers13102351. View

11.

Adamczyk-Gruszka O, Horecka-Lewitowicz A, Gruszka J, Wawszczak-Kasza M, Strzelecka A, Lewitowicz P . Endometrial Cancer in Aspect of Forkhead Box Protein Contribution. Int J Environ Res Public Health. 2022; 19(16). PMC: 9408638. DOI: 10.3390/ijerph191610403. View

12.

Cruz R, Madden S, Richards C, Vellanki S, Jahns H, Hudson L . Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1. Cancers (Basel). 2021; 13(4). PMC: 7922773. DOI: 10.3390/cancers13040871. View

13.

Ferguson H, Smith M, Francavilla C . Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling. Cells. 2021; 10(5). PMC: 8156822. DOI: 10.3390/cells10051201. View

14.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

15.

Sobocan M, Smolle M, Schatz C, Haybaeck J . The Interplay of Tumor Stroma and Translational Factors in Endometrial Cancer. Cancers (Basel). 2020; 12(8). PMC: 7463731. DOI: 10.3390/cancers12082074. View

16.

Ijichi N, Ikeda K, Horie-Inoue K, Inoue S . FOXP1 and estrogen signaling in breast cancer. Vitam Horm. 2013; 93:203-12. DOI: 10.1016/B978-0-12-416673-8.00006-X. View

17.

Zheng Z, Kang H, Lee S, Kang S, Goo B, Cho S . Up-regulation of fibroblast growth factor (FGF) 9 expression and FGF-WNT/β-catenin signaling in laser-induced wound healing. Wound Repair Regen. 2014; 22(5):660-5. DOI: 10.1111/wrr.12212. View

18.

Byron S, Gartside M, Powell M, Wellens C, Gao F, Mutch D . FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features. PLoS One. 2012; 7(2):e30801. PMC: 3285611. DOI: 10.1371/journal.pone.0030801. View

19.

Chen H, Chiang Y, Huang J, Huang T, Shih Y, Wang K . Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer. Cancers (Basel). 2021; 13(6). PMC: 8001359. DOI: 10.3390/cancers13061236. View

20.

Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H . Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol. 2017; 30(9):1299-1311. DOI: 10.1038/modpathol.2017.46. View