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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Research Article

Expression Profiling of EMT Transcriptional Regulators ZEB1 and ZEB2 in Different Histopathological Grades of Oral Squamous Cell Carcinoma Patients

Author(s): Neha Baqai, Rafat Amin*, Tehseen Fatima, Zeba Ahmed and Nousheen Faiz

Volume 25, Issue 2, 2024

Published on: 15 February, 2024

Page: [140 - 151] Pages: 12

DOI: 10.2174/0113892029284920240212091903

Price: $65

Abstract

Background: Pakistan has a high burden of oral cancers, with a prevalence rate of around 9%. Oral Squamous Cell Carcinoma (OSCC) accounts for about 90% of oral cancer cases. Epithelial to Mesenchymal Transition (EMT) gets highly stimulated in tumor cells by adopting subsequent malignant features of highly invasive cancer populations. Zinc Finger E-Box binding factors, ZEB1 and ZEB2, are regulatory proteins that promote EMT by suppressing the adherent ability of cells transforming into highly motile cancerous cells. The present study aimed to analyze the expression of EMT regulators, ZEB1 and ZEB2, and their association with the clinicopathological features in different grades of OSCC patients.

Methods: Tissue samples were collected for both case and control groups from the recruited study participants. Cancer tissues (cases) were collected from the confirmed OSCC patients, and healthy tissues (controls) were collected from third-molar dental extraction patients. The study participants were recruited with informed consent and brief demographic and clinical characteristics. The case group was further segregated with respect to the histological cancer grading system into well-differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD) squamous cell carcinoma (SCC) groups. RNA was extracted from the tissue samples for expression profiling of ZEB1 and ZEB2 genes through quantitative real-time PCR (qRT-PCR).

Results: All of the recruited participants had a mean age of 46.55 ± 11.7 (years), with most of them belonging to Urdu speaking ethnic group and were married. The BMI (kg/m2) of the healthy participants was in the normal range (18-22 kg/m2). However, BMI was found to be reduced with the proliferation in the pathological state of cancer. The oral hygiene of patients was better than the healthy participants, possibly due to the strict oral hygiene practice concerns of consultants. Every recruited OSCC patient had one or multiple addiction habits for more than a year. Patients reported health frailty (46.6%), unhealed mouth sores (40%), swallowing difficulties and white/reddish marks (80%), and restricted mouth opening (64.4%). Furthermore, 82.2% of the recruited patients observed symptoms within 1-12 months, and buccal mucosa was the most exposed tumor site among 55.6% of the patients. Expression profiling of EMT regulators showed gradual over-expressions of ZEB1 (8, 20, and 42 folds) and ZEB2 (4, 10, and 18 folds) in respective histological cancer grades.

Conclusion: High expressions of ZEBs have been significantly associated with cancer progression and poor health. However, no association was found between OSCC with other clinicopathological features when compared to healthy controls.

Graphical Abstract

[1]
Ciantelli, N.M.M.; Yoong, J.; Deschamps, J.; Jaqua, E.E. Exploring the interplay between lifestyle medicine and oral health: A bidirectional relationship. Am. J. Lifestyle Med., 2023, 15598276231213339.
[http://dx.doi.org/10.1177/15598276231213339]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L. Siegel, global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660]
[3]
Ferlay, J. Global cancer Observatory: cancer today; International Agency For Research On Cancer: Lyon, France, 2018.
[4]
Idrees, R.; Fatima, S.; Abdul-Ghafar, J.; Raheem, A.; Ahmad, Z. Cancer prevalence in Pakistan: Meta-analysis of various published studies to determine variation in cancer figures resulting from marked population heterogeneity in different parts of the country. World J. Surg. Oncol., 2018, 16(1), 129.
[http://dx.doi.org/10.1186/s12957-018-1429-z] [PMID: 29976196]
[5]
Pervez, S. Karachi Cancer Registry (KCR): Consolidated data of 5-years 2017-2021. J Coll Physicians Surg Pak, 2023, 33(5), 560-565.
[6]
Qureshi, M.A.; Mirza, T.; Khan, S.; Sikandar, B.; Zahid, M.; Aftab, M.; Mohsin, S.; Sharafat, S.; Avesi, L.; Hassan, S. Cancer patterns in Karachi (all districts), Pakistan: First results (2010–2015) from a pathology based cancer registry of the largest government-run diagnostic and reference center of Karachi. Cancer Epidemiol., 2016, 44, 114-122.
[http://dx.doi.org/10.1016/j.canep.2016.08.011] [PMID: 27566468]
[7]
Pervez, S.; Jabbar, A.A.; Haider, G.; Ashraf, S.; Qureshi, M.; Lateef, F.; Bashir, I.; Zaidi, M.; Khurshid, M.; Quraishy, M.; Siddiqi, T.; Rizwan, U.; Saqib, M.A.; Memon, M.; Alam, E.; Qureshi, H. Karachi cancer registry (KCR): Age-standardized incidence rate by age-group and gender in a mega city of Pakistan. Asian Pac. J. Cancer Prev., 2020, 21(11), 3251-3258.
[http://dx.doi.org/10.31557/APJCP.2020.21.11.3251] [PMID: 33247682]
[8]
Badwelan, M.; Muaddi, H.; Ahmed, A.; Lee, K.T.; Tran, S.D. Oral squamous cell carcinoma and concomitant primary tumors, what do we know? a review of the literature. Curr. Oncol., 2023, 30(4), 3721-3734.
[http://dx.doi.org/10.3390/curroncol30040283] [PMID: 37185396]
[9]
Bibi, K.; Fatima, T.; Sohrab, S.; Haider, G.; Zarina, S.; Ilyas, A. Polymorphic variants of ASS1 gene related to arginine metabolism and the risk of HCC. Protein Pept. Lett., 2023, 30(7), 587-596.
[http://dx.doi.org/10.2174/0929866530666230529143121] [PMID: 37254538]
[10]
Ullah, A.; Razzaq, A.; Zhou, C.; Ullah, N.; Shehzadi, S.; Aziz, T.; Alfaifi, M.Y.; Elbehairi, S.E.I.; Iqbal, H. Biological significance of ephb4 expression in cancer. Curr. Protein Pept. Sci., 2023, 24
[http://dx.doi.org/10.2174/0113892037269589231017055642] [PMID: 37909437]
[11]
Ullah, A.; Shehzadi, S.; Ullah, N.; Nawaz, T.; Iqbal, H.; Aziz, T. Hypoxia a typical target in human lung cancer therapy. Curr. Protein Pept. Sci., 2023, 24
[http://dx.doi.org/10.2174/0113892037252820231114045234] [PMID: 38031268]
[12]
Cheng, Y.S.L.; Rees, T.; Wright, J. A review of research on salivary biomarkers for oral cancer detection. Clin. Transl. Med., 2014, 3(1), e3.
[http://dx.doi.org/10.1186/2001-1326-3-3] [PMID: 24564868]
[13]
Gulati, A.; Sobti, R. Oral squamous cell carcinoma. In: Biomarkers in Cancer Detection and Monitoring of Therapeutics; Elsevier, 2024; pp. 1-87.
[http://dx.doi.org/10.1016/B978-0-323-95114-2.00008-X]
[14]
Tumban, E. A current update on human papillomavirus‐associated head and neck cancers. Viruses, 2019, 11(10), 922.
[http://dx.doi.org/10.3390/v11100922] [PMID: 31600915]
[15]
Lei, Z.N.; Tian, Q.; Teng, Q.X.; Wurpel, J.N.D.; Zeng, L.; Pan, Y.; Chen, Z.S. Understanding and targeting resistance mechanisms in cancer. MedComm, 2023, 4(3), e265.
[http://dx.doi.org/10.1002/mco2.265] [PMID: 37229486]
[16]
Ling, Z.; Cheng, B.; Tao, X. Epithelial-to-mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities. Int. J. Cancer, 2021, 148(7), 1548-1561.
[http://dx.doi.org/10.1002/ijc.33352] [PMID: 33091960]
[17]
Ang, H.L.; Mohan, C.D.; Shanmugam, M.K.; Leong, H.C.; Makvandi, P.; Rangappa, K.S.; Bishayee, A.; Kumar, A.P.; Sethi, G. Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds. Med. Res. Rev., 2023, 43(4), 1141-1200.
[http://dx.doi.org/10.1002/med.21948] [PMID: 36929669]
[18]
Akhurst, R.J. From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition. In: Seminars in Cancer Biology; Elsevier, 2023.
[http://dx.doi.org/10.1016/j.semcancer.2023.10.003]
[19]
Georgakopoulos-Soares, I.; Chartoumpekis, D.V.; Kyriazopoulou, V.; Zaravinos, A. EMT factors and metabolic pathways in cancer. Front. Oncol., 2020, 10, 499.
[http://dx.doi.org/10.3389/fonc.2020.00499] [PMID: 32318352]
[20]
Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest., 2009, 119(6), 1420-1428.
[http://dx.doi.org/10.1172/JCI39104] [PMID: 19487818]
[21]
Lamouille, S.; Xu, J.; Derynck, R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol., 2014, 15(3), 178-196.
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[22]
Vandewalle, C.; Van Roy, F.; Berx, G. The role of the ZEB family of transcription factors in development and disease. Cell. Mol. Life Sci., 2009, 66(5), 773-787.
[http://dx.doi.org/10.1007/s00018-008-8465-8] [PMID: 19011757]
[23]
Davies, A.; Zoubeidi, A.; Beltran, H.; Selth, L.A. The transcriptional and epigenetic landscape of cancer cell lineage plasticity. Cancer Discov., 2023, 13(8), 1771-1788.
[http://dx.doi.org/10.1158/2159-8290.CD-23-0225] [PMID: 37470668]
[24]
Ciriello, G. Cancer evolution: A multifaceted affair. Cancer Discov., 2023, 14(1), 36-48.
[PMID: 38047596]
[25]
Kang, N.; Xie, X.; Zhou, X.; Wang, Y.; Chen, S.; Qi, R.; Liu, T.; Jiang, H. Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer. BMC Gastroenterol., 2022, 22(1), 190.
[http://dx.doi.org/10.1186/s12876-022-02257-2] [PMID: 35429970]
[26]
Chaffer, C.L.; Weinberg, R.A. A perspective on cancer cell metastasis. Science, 2011, 331(6024), 1559-1564.
[http://dx.doi.org/10.1126/science.1203543]
[27]
Derynck, R.; Weinberg, R.A. EMT and cancer: More than meets the eye. Dev. Cell, 2019, 49(3), 313-316.
[http://dx.doi.org/10.1016/j.devcel.2019.04.026] [PMID: 31063750]
[28]
Edme, N.; Downward, J.; Thiery, J.P.; Boyer, B. Ras induces NBT-II epithelial cell scattering through the coordinate activities of Rac and MAPK pathways. J. Cell Sci., 2002, 115(12), 2591-2601.
[http://dx.doi.org/10.1242/jcs.115.12.2591] [PMID: 12045229]
[29]
Göppel, J.; Möckelmann, N.; Münscher, A.; Sauter, G.; Schumacher, U. Expression of epithelial-mesenchymal transition regulating transcription factors in head and neck squamous cell carcinomas. Anticancer Res., 2017, 37(10), 5435-5440.
[PMID: 28982853]
[30]
Sreeshma, B. Unravelling the crosstalk of Hedgehog with Wnt, Notch and TGF-β signaling pathways. In: Stem Cells and Signaling Pathways; Elsevier, 2024; pp. 181-203.
[http://dx.doi.org/10.1016/B978-0-443-18800-8.00001-0]
[31]
Zhou, Y.; Sun, S.; Ling, T.; Chen, Y.; Zhou, R.; You, Q. The role of fibroblast growth factor 18 in cancers: Functions and signaling pathways. Front. Oncol., 2023, 13, 1124520.
[http://dx.doi.org/10.3389/fonc.2023.1124520] [PMID: 37228502]
[32]
Atwell, B.; Chen, C.Y.; Christofferson, M.; Montfort, W.R.; Schroeder, J. Sorting nexin-dependent therapeutic targeting of oncogenic epidermal growth factor receptor. Cancer Gene Ther., 2023, 30(2), 267-276.
[http://dx.doi.org/10.1038/s41417-022-00541-7] [PMID: 36253541]
[33]
Uckun, F.M.; Qazi, S.; Trieu, V. High intra-tumor transforming growth factor beta 2 level as a predictor of poor treatment outcomes in pediatric diffuse intrinsic pontine glioma. Cancers, 2023, 15(6), 1676.
[http://dx.doi.org/10.3390/cancers15061676] [PMID: 36980562]
[34]
Alkhathami, A.G.; Abdullah, M.R.; Ahmed, M.; Ahmed, H.H.; Alwash, S.W.; Mahdi, M.Z.; Alsaikhan, F.; Dera, A.A. Bone morphogenetic protein (BMP)9 in cancer development: Mechanistic, diagnostic, and therapeutic approaches? J. Drug Target., 2023, 31(7), 714-724.
[http://dx.doi.org/10.1080/1061186X.2023.2236330] [PMID: 37461888]
[35]
soleymani, L.; Zarrabi, A.; Hashemi, F.; Hashemi, F.; Zabolian, A.; Banihashemi, S.M.; Moghadam, S.S.; Hushmandi, K.; Samarghandian, S.; Ashrafizadeh, M.; Khan, H. Role of ZEB family members in proliferation, metastasis, and chemoresistance of prostate cancer cells: revealing signaling networks. Curr. Cancer Drug Targets, 2021, 21(9), 749-767.
[http://dx.doi.org/10.2174/1568009621666210601114631] [PMID: 34077345]
[36]
Das, V.; Bhattacharya, S.; Chikkaputtaiah, C.; Hazra, S.; Pal, M. The basics of epithelial–mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective. J. Cell. Physiol., 2019, 234(9), 14535-14555.
[http://dx.doi.org/10.1002/jcp.28160] [PMID: 30723913]
[37]
Stemmler, M.P.; Eccles, R.L.; Brabletz, S.; Brabletz, T. Non-redundant functions of EMT transcription factors. Nat. Cell Biol., 2019, 21(1), 102-112.
[http://dx.doi.org/10.1038/s41556-018-0196-y] [PMID: 30602760]
[38]
Tan, Y.; Wang, Z.; Xu, M.; Li, B.; Huang, Z.; Qin, S.; Nice, E.C.; Tang, J.; Huang, C. Oral squamous cell carcinomas: State of the field and emerging directions. Int. J. Oral Sci., 2023, 15(1), 44.
[http://dx.doi.org/10.1038/s41368-023-00249-w] [PMID: 37736748]
[39]
Saitoh, M. Transcriptional regulation of EMT transcription factors in cancer. In: Seminars in Cancer Biology; Elsevier, 2023.
[http://dx.doi.org/10.1016/j.semcancer.2023.10.001]
[40]
Waryah, C.; Alves, E.; Mazzieri, R.; Dolcetti, R.; Thompson, E.W.; Redfern, A.; Blancafort, P. Unpacking the complexity of epithelial plasticity: From master regulator transcription factors to non-coding RNAs. Cancers, 2023, 15(12), 3152.
[http://dx.doi.org/10.3390/cancers15123152] [PMID: 37370762]
[41]
Li, D.; Xia, L.; Huang, P.; Wang, Z.; Guo, Q.; Huang, C.; Leng, W.; Qin, S. Heterogeneity and plasticity of epithelial–mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms. Cell Prolif., 2023, 56(6), e13423.
[http://dx.doi.org/10.1111/cpr.13423] [PMID: 36808651]
[42]
Cho, E.S.; Kang, H.E.; Kim, N.H.; Yook, J.I. Therapeutic implications of cancer epithelial-mesenchymal transition (EMT). Arch. Pharm. Res., 2019, 42(1), 14-24.
[http://dx.doi.org/10.1007/s12272-018-01108-7] [PMID: 30649699]
[43]
Li, J.; Riedt, T.; Goossens, S.; Carrillo García, C.; Szczepanski, S.; Brandes, M.; Pieters, T.; Dobrosch, L.; Gütgemann, I.; Farla, N.; Radaelli, E.; Hulpiau, P.; Mallela, N.; Fröhlich, H.; La Starza, R.; Matteucci, C.; Chen, T.; Brossart, P.; Mecucci, C.; Huylebroeck, D.; Haigh, J.J.; Janzen, V. The EMT transcription factor Zeb2 controls adult murine hematopoietic differentiation by regulating cytokine signaling. Blood, 2017, 129(4), 460-472.
[http://dx.doi.org/10.1182/blood-2016-05-714659] [PMID: 27683414]
[44]
Hanrahan, K.; O’Neill, A.; Prencipe, M.; Bugler, J.; Murphy, L.; Fabre, A.; Puhr, M.; Culig, Z.; Murphy, K.; Watson, R.W. The role of epithelial–mesenchymal transition drivers ZEB 1 and ZEB 2 in mediating docetaxel‐resistant prostate cancer. Mol. Oncol., 2017, 11(3), 251-265.
[http://dx.doi.org/10.1002/1878-0261.12030] [PMID: 28133913]
[45]
Ang, L.; Zheng, L.; Wang, J.; Huang, J.; Hu, H.G.; Zou, Q.; Zhao, Y.; Liu, Q.M.; Zhao, M.; Wu, Z.S. Expression of and correlation between BCL6 and ZEB family members in patients with breast cancer. Exp. Ther. Med., 2017, 14(5), 3985-3992.
[http://dx.doi.org/10.3892/etm.2017.5101] [PMID: 29104620]
[46]
Arima, Y.; Hayashi, H.; Sasaki, M.; Hosonaga, M.; Goto, T.M.; Chiyoda, T.; Kuninaka, S.; Shibata, T.; Ohata, H.; Nakagama, H.; Taya, Y.; Saya, H. Induction of ZEB proteins by inactivation of RB protein is key determinant of mesenchymal phenotype of breast cancer. J. Biol. Chem., 2012, 287(11), 7896-7906.
[http://dx.doi.org/10.1074/jbc.M111.313759] [PMID: 22262832]
[47]
Kim, H.R.; Seo, C.W.; Han, S.J. Zinc finger e-box binding homeobox 2 as a prognostic biomarker in various cancers and its correlation with infiltrating immune cells in ovarian cancer. Curr Issues Mol Biol., 2022, 44(3), 1203-1214.
[http://dx.doi.org/10.3390/cimb44030079]
[48]
Hurt, E.M.; Saykally, J.N.; Anose, B.M.; Kalli, K.R.; Sanders, M.M. Expression of the ZEB1 (δEF1) transcription factor in human: Additional insights. Mol. Cell. Biochem., 2008, 318(1-2), 89-99.
[http://dx.doi.org/10.1007/s11010-008-9860-z] [PMID: 18622689]
[49]
Li, Y.; Fei, H.; Lin, Q.; Liang, F.; You, Y.; Li, M.; Wu, M.; Qu, Y.; Li, P.; Yuan, Y.; Chen, T.; Jiang, H. ZEB2 facilitates peritoneal metastasis by regulating the invasiveness and tumorigenesis of cancer stem-like cells in high-grade serous ovarian cancers. Oncogene, 2021, 40(32), 5131-5141.
[http://dx.doi.org/10.1038/s41388-021-01913-3] [PMID: 34211089]
[50]
Yao, X.; Sun, S.; Zhou, X.; Zhang, Q.; Guo, W.; Zhang, L. Clinicopathological significance of ZEB-1 and E-cadherin proteins in patients with oral cavity squamous cell carcinoma. OncoTargets Ther., 2017, 10, 781-790.
[http://dx.doi.org/10.2147/OTT.S111920] [PMID: 28243114]
[51]
Kong, Y.H.; Syed Zanaruddin, S.N.; Lau, S.H.; Ramanathan, A.; Kallarakkal, T.G.; Vincent-Chong, V.K.; Wan Mustafa, W.M.; Abraham, M.T.; Rahman, A.Z.A.; Zain, R.B.; Cheong, S.C. Co-expression of TWIST1 and ZEB2 in oral squamous cell carcinoma is associated with poor survival. PLoS One, 2015, 10(7), e0134045.
[http://dx.doi.org/10.1371/journal.pone.0134045] [PMID: 26214683]
[52]
Bustin, S.A. The MIQE Guidelines: M inimum I nformation for Publication of Q uantitative Real-Time PCR E xperiments; Oxford University Press, 2009.
[53]
Natarajan, E. Oral and oropharyngeal cancer. In: Dental Science for the Medical Professional; , 2023; pp. 261-301.
[http://dx.doi.org/10.1007/978-3-031-38567-4_19]
[54]
Odell, E.; Kujan, O.; Warnakulasuriya, S.; Sloan, P. Oral epithelial dysplasia: Recognition, grading and clinical significance. Oral Dis., 2021, 27(8), 1947-1976.
[http://dx.doi.org/10.1111/odi.13993] [PMID: 34418233]
[55]
Woo, S.B. Oral epithelial dysplasia and premalignancy. Head Neck Pathol., 2019, 13(3), 423-439.
[http://dx.doi.org/10.1007/s12105-019-01020-6] [PMID: 30887394]
[56]
Abati, S.; Bramati, C.; Bondi, S.; Lissoni, A.; Trimarchi, M. Oral cancer and precancer: A narrative review on the relevance of early diagnosis. Int. J. Environ. Res. Public Health, 2020, 17(24), 9160.
[http://dx.doi.org/10.3390/ijerph17249160] [PMID: 33302498]
[57]
Rivera, C.; Venegas, B. Histological and molecular aspects of oral squamous cell carcinoma (Review). Oncol. Lett., 2014, 8(1), 7-11.
[http://dx.doi.org/10.3892/ol.2014.2103] [PMID: 24959211]
[58]
Speight, P.M.; Takata, T. New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: Odontogenic and maxillofacial bone tumours. Virchows Archiv, 2018, 472(3), 331-339.
[59]
Anwar, N.; Pervez, S.; Chundriger, Q.; Awan, S.; Moatter, T.; Ali, T.S. Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan. PLoS One, 2020, 15(8), e0236359.
[http://dx.doi.org/10.1371/journal.pone.0236359] [PMID: 32760151]
[60]
Wolfer, S.; Foos, T.; Kunzler, A.; Ernst, C.; Schultze-Mosgau, S. Association of the preoperative body mass index with postoperative complications after treatment of oral squamous cell carcinoma. J. Oral Maxillofac. Surg., 2018, 76(8), 1800-1815.
[http://dx.doi.org/10.1016/j.joms.2018.02.029] [PMID: 29605536]
[61]
Wang, C.; Pan, Y.; Xu, Q.; Li, B.; Kim, K.; Mao, M.; Li, J.; Qin, L.; Li, H.; Han, Z.; Feng, Z. Relationship between body mass index and outcomes for patients with oral squamous cell carcinoma. Oral Dis., 2019, 25(1), 87-96.
[http://dx.doi.org/10.1111/odi.12963] [PMID: 30144246]
[62]
Elebyary, O.; Barbour, A.; Fine, N.; Tenenbaum, H.C.; Glogauer, M. The crossroads of periodontitis and oral squamous cell carcinoma: Immune implications and tumor promoting capacities. Frontiers in Oral Health, 2021, 1, 584705.
[http://dx.doi.org/10.3389/froh.2020.584705] [PMID: 35047982]
[63]
Shrestha, A.D.; Vedsted, P.; Kallestrup, P.; Neupane, D. Prevalence and incidence of oral cancer in low- and middle-income countries: A scoping review. Eur. J. Cancer Care, 2020, 29(2), e13207.
[http://dx.doi.org/10.1111/ecc.13207] [PMID: 31820851]
[64]
Lin, N.C.; Hsu, J.T.; Tsai, K.Y. Survival and clinicopathological characteristics of different histological grades of oral cavity squamous cell carcinoma: A single-center retrospective study. PLoS One, 2020, 15(8), e0238103.
[http://dx.doi.org/10.1371/journal.pone.0238103] [PMID: 32841288]
[65]
Ettinger, K.S.; Ganry, L.; Fernandes, R.P. Oral cavity cancer. Oral Maxillofac. Surg. Clin. North Am., 2019, 31(1), 13-29.
[http://dx.doi.org/10.1016/j.coms.2018.08.002] [PMID: 30454788]
[66]
Do, W.; Elzerman, T.; de Bree, R.; Rosenberg, A.; Forouzanfar, T.; Van Cann, E.M. Is low or high body mass index in patients operated for oral squamous cell carcinoma associated with the perioperative complication rate? Int. J. Oral Maxillofac. Surg., 2021, 50(5), 591-597.
[http://dx.doi.org/10.1016/j.ijom.2020.07.023] [PMID: 32861557]
[67]
Bagan, J.; Sarrion, G.; Jimenez, Y. Oral cancer: Clinical features. Oral Oncol., 2010, 46(6), 414-417.
[http://dx.doi.org/10.1016/j.oraloncology.2010.03.009] [PMID: 20400366]
[68]
Tadbir, A.A.; Ebrahimi, H.; Pourshahidi, S.; Zeraatkar, M. Evaluation of levels of knowledge about etiology and symptoms of oral cancer in southern Iran. Asian Pac. J. Cancer Prev., 2013, 14(4), 2217-2220.
[http://dx.doi.org/10.7314/APJCP.2013.14.4.2217] [PMID: 23725115]
[69]
Cuffari, L.; Siqueira, J.T.T.; Nemr, K.; Rapaport, A. Pain complaint as the first symptom of oral cancer: A descriptive study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2006, 102(1), 56-61.
[http://dx.doi.org/10.1016/j.tripleo.2005.10.041] [PMID: 16831673]
[70]
Giovannucci, E.; Stampfer, M.J.; Krithivas, K.; Brown, M.; Brufsky, A.; Talcott, J.; Hennekens, C.H.; Kantoff, P.W.; Kantoff, P.W. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl. Acad. Sci., 1997, 94(7), 3320-3323.
[http://dx.doi.org/10.1073/pnas.94.7.3320] [PMID: 9096391]
[71]
Xue, C.; Plieth, D.; Venkov, C.; Xu, C.; Neilson, E.G. The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res., 2003, 63(12), 3386-3394.
[PMID: 12810675]
[72]
Chaw, S.Y.; Abdul Majeed, A.; Dalley, A.J.; Chan, A.; Stein, S.; Farah, C.S. Epithelial to mesenchymal transition (EMT) biomarkers – E-cadherin, beta-catenin, APC and Vimentin – in oral squamous cell carcinogenesis and transformation. Oral Oncol., 2012, 48(10), 997-1006.
[http://dx.doi.org/10.1016/j.oraloncology.2012.05.011] [PMID: 22704062]
[73]
Slean, M.M.; Panigrahi, G.B.; Castel, A.L.; Pearson, A.B.; Tomkinson, A.E.; Pearson, C.E. Absence of MutSβ leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks. DNA Repair, 2016, 42, 107-118.
[http://dx.doi.org/10.1016/j.dnarep.2016.04.002] [PMID: 27155933]
[74]
Jia, B.; Liu, H.; Kong, Q.; Li, B. Overexpression of ZEB1 associated with metastasis and invasion in patients with gastric carcinoma. Mol. Cell. Biochem., 2012, 366(1-2), 223-229.
[http://dx.doi.org/10.1007/s11010-012-1299-6] [PMID: 22466758]
[75]
Gemmill, R.M.; Roche, J.; Potiron, V.A.; Nasarre, P.; Mitas, M.; Coldren, C.D.; Helfrich, B.A.; Garrett-Mayer, E.; Bunn, P.A.; Drabkin, H.A. ZEB1-responsive genes in non-small cell lung cancer. Cancer Lett., 2011, 300(1), 66-78.
[http://dx.doi.org/10.1016/j.canlet.2010.09.007] [PMID: 20980099]
[76]
Shen, A.; Zhang, Y.; Yang, H.; Xu, R.; Huang, G. Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. J. Surg. Oncol., 2012, 105(8), 830-834.
[http://dx.doi.org/10.1002/jso.23012] [PMID: 22213004]
[77]
Larsen, J.E.; Nathan, V.; Osborne, J.K.; Farrow, R.K.; Deb, D.; Sullivan, J.P.; Dospoy, P.D.; Augustyn, A.; Hight, S.K.; Sato, M.; Girard, L.; Behrens, C.; Wistuba, I.I.; Gazdar, A.F.; Hayward, N.K.; Minna, J.D. ZEB1 drives epithelial-to-mesenchymal transition in lung cancer. J. Clin. Invest., 2016, 126(9), 3219-3235.
[http://dx.doi.org/10.1172/JCI76725] [PMID: 27500490]
[78]
Kahlert, C.; Lahes, S.; Radhakrishnan, P.; Dutta, S.; Mogler, C.; Herpel, E.; Brand, K.; Steinert, G.; Schneider, M.; Mollenhauer, M.; Reissfelder, C.; Klupp, F.; Fritzmann, J.; Wunder, C.; Benner, A.; Kloor, M.; Huth, C.; Contin, P.; Ulrich, A.; Koch, M.; Weitz, J. Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro. Clin. Cancer Res., 2011, 17(24), 7654-7663.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2816] [PMID: 22042972]
[79]
Fardi, M.; Alivand, M.; Baradaran, B.; Farshdousti Hagh, M.; Solali, S. The crucial role of ZEB2: From development to epithelial‐to‐mesenchymal transition and cancer complexity. J. Cell. Physiol., 2019, 234(9), 14783-14799.
[http://dx.doi.org/10.1002/jcp.28277] [PMID: 30773635]
[80]
Li, M-Z.; Wang, J.J.; Yang, S.B.; Li, W.F.; Xiao, L.B.; He, Y.L.; Song, X.M. ZEB2 promotes tumor metastasis and correlates with poor prognosis of human colorectal cancer. Am. J. Transl. Res., 2017, 9(6), 2838-2851.
[PMID: 28670373]
[81]
Kurahara, H.; Takao, S.; Maemura, K.; Mataki, Y.; Kuwahata, T.; Maeda, K.; Ding, Q.; Sakoda, M.; Iino, S.; Ishigami, S.; Ueno, S.; Shinchi, H.; Natsugoe, S. Epithelial–mesenchymal transition and mesenchymal–epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer. J. Surg. Oncol., 2012, 105(7), 655-661.
[http://dx.doi.org/10.1002/jso.23020] [PMID: 22213144]

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