Skip to main content
Top
Published in: International Journal of Clinical Oncology 6/2020

01-06-2020 | Oral Cancer | Original Article

Down-regulation of miR-200c associates with poor prognosis of oral squamous cell carcinoma

Authors: Jian Song, Nian Zhang, Lideng Cao, Di Xiao, Xingchen Ye, En Luo, Zhuang Zhang

Published in: International Journal of Clinical Oncology | Issue 6/2020

Login to get access

Abstract

Background

MicroRNAs (miRNAs) are considered as promising cancer biomarkers. The aim of the present study is to investigate the prognostic significance of miR-200c in patients with oral squamous cell carcinoma (OSCC).

Materials and methods

Quantitative real-time PCR (qRT-PCR) was used to determine the expression levels of miR-200c in 204 pairs of OSCC and adjacent noncancerous. Correlations between miR-200c expression levels and clinicopathological characteristics were investigated. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Multivariate analysis of the prognostic factors was performed with a Cox proportional hazards regression model.

Results

The expression of miR-200c was significantly down-regulated in OSCC tissues compared with adjacent non-tumor tissues (p < 0.0001). Low expression of miR-200c in tumor tissues was significantly correlated with the positive N classification (p = 0.013), advanced TNM stage (p = 0.007) and poor differentiation grade (p = 0.026). Lower miR-200c expression in patients was significantly associated with poor recurrence-free survival (RFS, p = 0.0003) and overall survival (OS, p = 0.0026). Multivariate analysis confirmed that low miR-200c expression was an independent predictor for poor RFS (hazard ratio (HR) 1.705, 95% CI 1.136–2.56, p = 0.01) and OS (HR 1.669, 95% CI 1.03–2.703, p = 0.037) in patients with OSCC.

Conclusion

Our results suggest that the miR-200c might be a potential prognostic biomarker for OSCC.
Literature
1.
go back to reference Zhao X, Sun S, Zeng X et al (2018) Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma. Am J Cancer Res 8(3):450–461PubMedPubMedCentral Zhao X, Sun S, Zeng X et al (2018) Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma. Am J Cancer Res 8(3):450–461PubMedPubMedCentral
3.
go back to reference Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424CrossRefPubMed Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424CrossRefPubMed
4.
go back to reference Singhvi HR, Malik A, Chaturvedi P (2017) The role of chronic mucosal trauma in oral cancer: a review of literature. Indian J Med Paediatr Oncol 38(1):44–50CrossRefPubMedPubMedCentral Singhvi HR, Malik A, Chaturvedi P (2017) The role of chronic mucosal trauma in oral cancer: a review of literature. Indian J Med Paediatr Oncol 38(1):44–50CrossRefPubMedPubMedCentral
5.
6.
go back to reference Woolgar JA, Hall GL (2009) Determinants of outcome following surgery for oral squamous cell carcinoma. Future Oncol 5(1):51–61CrossRefPubMed Woolgar JA, Hall GL (2009) Determinants of outcome following surgery for oral squamous cell carcinoma. Future Oncol 5(1):51–61CrossRefPubMed
8.
go back to reference Macfarlane LA, Murphy PR (2010) MicroRNA: biogenesis, function and role in cancer. Curr Genom 11(7):537–561CrossRef Macfarlane LA, Murphy PR (2010) MicroRNA: biogenesis, function and role in cancer. Curr Genom 11(7):537–561CrossRef
10.
go back to reference Irani S (2016) miRNAs signature in head and neck squamous cell carcinoma metastasis: a literature review. J Dent (Shiraz) 17(2):71–83 Irani S (2016) miRNAs signature in head and neck squamous cell carcinoma metastasis: a literature review. J Dent (Shiraz) 17(2):71–83
11.
go back to reference Jakob M, Mattes LM, Küffer S et al (2019) MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer. Head Neck 41(10):3499–3515CrossRefPubMed Jakob M, Mattes LM, Küffer S et al (2019) MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer. Head Neck 41(10):3499–3515CrossRefPubMed
12.
go back to reference Shi J, Bao X, Liu Z et al (2019) Serum miR-626 and miR-5100 are promising prognosis predictors for oral squamous cell carcinoma. Theranostics 9(4):920–931CrossRefPubMedPubMedCentral Shi J, Bao X, Liu Z et al (2019) Serum miR-626 and miR-5100 are promising prognosis predictors for oral squamous cell carcinoma. Theranostics 9(4):920–931CrossRefPubMedPubMedCentral
13.
go back to reference Baba O, Hasegawa S, Nagai H et al (2016) MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med 45(4):248–255CrossRefPubMed Baba O, Hasegawa S, Nagai H et al (2016) MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med 45(4):248–255CrossRefPubMed
14.
go back to reference Park SM, Gaur AB, Lengyel E et al (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907CrossRefPubMedPubMedCentral Park SM, Gaur AB, Lengyel E et al (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907CrossRefPubMedPubMedCentral
15.
go back to reference Wong CM, Wei L, Au SL et al (2015) MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis. Oncotarget 6(15):13658–13670CrossRefPubMedPubMedCentral Wong CM, Wei L, Au SL et al (2015) MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis. Oncotarget 6(15):13658–13670CrossRefPubMedPubMedCentral
16.
go back to reference Zhang JY, Wang YM, Song LB et al (2016) Prognostic significance of microRNA-200c in various types of cancer: an updated meta-analysis of 34 studies. Mol Clin Oncol 4(6):933–941CrossRefPubMedPubMedCentral Zhang JY, Wang YM, Song LB et al (2016) Prognostic significance of microRNA-200c in various types of cancer: an updated meta-analysis of 34 studies. Mol Clin Oncol 4(6):933–941CrossRefPubMedPubMedCentral
17.
go back to reference Patel S, Shah K, Mirza S et al (2015) Epigenetic regulators governing cancer stem cells and epithelial-mesenchymal transition in oral squamous cell carcinoma. Curr Stem Cell Res Ther 10(2):140–152CrossRefPubMed Patel S, Shah K, Mirza S et al (2015) Epigenetic regulators governing cancer stem cells and epithelial-mesenchymal transition in oral squamous cell carcinoma. Curr Stem Cell Res Ther 10(2):140–152CrossRefPubMed
18.
go back to reference Kawakubo-Yasukochi T, Morioka M, Hazekawa M et al (2018) miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment. Mol Carcinog 57(2):295–302CrossRefPubMed Kawakubo-Yasukochi T, Morioka M, Hazekawa M et al (2018) miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment. Mol Carcinog 57(2):295–302CrossRefPubMed
19.
go back to reference Xie NN, Liu ZX, Wu C et al (2018) MicroRNA-200c suppresses tumor metastasis in oral squamous carcinoma by inhibiting epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci 22(11):3415–3422PubMed Xie NN, Liu ZX, Wu C et al (2018) MicroRNA-200c suppresses tumor metastasis in oral squamous carcinoma by inhibiting epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci 22(11):3415–3422PubMed
20.
go back to reference Yan Y, Yan F, Huang Q (2018) MiR-200c inhibited the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1. Arch Oral Biol 96:52–57CrossRefPubMed Yan Y, Yan F, Huang Q (2018) MiR-200c inhibited the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1. Arch Oral Biol 96:52–57CrossRefPubMed
21.
go back to reference Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China, (2016). CA Cancer J Clin 66(2):115–132CrossRefPubMed Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China, (2016). CA Cancer J Clin 66(2):115–132CrossRefPubMed
22.
23.
go back to reference Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 20(8):460–469CrossRefPubMed Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 20(8):460–469CrossRefPubMed
24.
go back to reference Jamali Z, Asl Aminabadi N, Attaran R et al (2015) MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol 51(4):321–331CrossRefPubMed Jamali Z, Asl Aminabadi N, Attaran R et al (2015) MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol 51(4):321–331CrossRefPubMed
25.
go back to reference Arunkumar G, Deva Magendhra Rao AK, Manikandan M et al (2018) Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma. Oncol Lett 15(1):649–657PubMed Arunkumar G, Deva Magendhra Rao AK, Manikandan M et al (2018) Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma. Oncol Lett 15(1):649–657PubMed
26.
go back to reference Chang CJ, Chao CH, Xia W et al (2011) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13(3):317–323CrossRefPubMedPubMedCentral Chang CJ, Chao CH, Xia W et al (2011) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13(3):317–323CrossRefPubMedPubMedCentral
28.
go back to reference Kim H, Yang JM, Ahn SH et al (2018) Potential oncogenic role and prognostic implication of microRNA-155-5p in oral squamous cell carcinoma. Anticancer Res 38(9):5193–5200CrossRefPubMed Kim H, Yang JM, Ahn SH et al (2018) Potential oncogenic role and prognostic implication of microRNA-155-5p in oral squamous cell carcinoma. Anticancer Res 38(9):5193–5200CrossRefPubMed
29.
go back to reference Wei D, Wang W, Shen B et al (2019) MicroRNA-199a-5p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMT-related transcription factor SOX4. Int J Mol Med 44(1):185–195PubMedPubMedCentral Wei D, Wang W, Shen B et al (2019) MicroRNA-199a-5p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMT-related transcription factor SOX4. Int J Mol Med 44(1):185–195PubMedPubMedCentral
30.
go back to reference Warnakulasuriya S (2020) Oral potentially malignant disorders: a comprehensive review on clinical aspects and management. Oral Oncol 102:104550CrossRefPubMed Warnakulasuriya S (2020) Oral potentially malignant disorders: a comprehensive review on clinical aspects and management. Oral Oncol 102:104550CrossRefPubMed
31.
go back to reference Mutlu M, Raza U, Saatci Ö et al (2016) miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med (Berl) 94(6):629–644CrossRef Mutlu M, Raza U, Saatci Ö et al (2016) miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med (Berl) 94(6):629–644CrossRef
32.
go back to reference Armand-Labit V, Pradines A (2017) Circulating cell-free microRNAs as clinical cancer biomarkers. Biomol Concepts 8(2):61–81CrossRefPubMed Armand-Labit V, Pradines A (2017) Circulating cell-free microRNAs as clinical cancer biomarkers. Biomol Concepts 8(2):61–81CrossRefPubMed
33.
go back to reference Jarry J, Schadendorf D, Greenwood C et al (2014) The validity of circulating microRNAs in oncology: five years of challenges and contradictions. Mol Oncol 8(4):819–829CrossRefPubMedPubMedCentral Jarry J, Schadendorf D, Greenwood C et al (2014) The validity of circulating microRNAs in oncology: five years of challenges and contradictions. Mol Oncol 8(4):819–829CrossRefPubMedPubMedCentral
Metadata
Title
Down-regulation of miR-200c associates with poor prognosis of oral squamous cell carcinoma
Authors
Jian Song
Nian Zhang
Lideng Cao
Di Xiao
Xingchen Ye
En Luo
Zhuang Zhang
Publication date
01-06-2020
Publisher
Springer Singapore
Published in
International Journal of Clinical Oncology / Issue 6/2020
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-020-01649-2

Other articles of this Issue 6/2020

International Journal of Clinical Oncology 6/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine