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. 2022 Dec;16(4):1134-1145.
doi: 10.1007/s12105-022-01475-0. Epub 2022 Aug 18.

Prognostic impact of MUC1 and potential regulatory miR-145 and miR-21 expression in salivary mucoepidermoid carcinoma

Ali Abdolrahmani  1 , Neda Kardouni Khoozestani  2   3   4 , Farid Azmoudeh-Ardalan  5   6 , Ahmad Reza Shamshiri  7
Affiliations

Prognostic impact of MUC1 and potential regulatory miR-145 and miR-21 expression in salivary mucoepidermoid carcinoma

Ali Abdolrahmani et al. Head Neck Pathol. 2022 Dec.

Abstract

Background: Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need for specifying prognostic biomarkers to identify patients who are in need of more intensive and prolonged follow-ups. This study aimed to assess the mucin 1 (MUC1) expression level and its potential regulatory microRNAs in salivary gland MEC and their prognostic potentials.

Materials and methods: The expression of MUC1 in salivary gland MEC tissues was assessed in 47 samples using immunohistochemistry. Related microRNA (miR-145 and miR-21) were evaluated using quantitative Reverse Transcription PCR. The associations between MUC1 and microRNAs expressions and clinicopathological parameters were investigated.

Results: MUC1 expression levels positively correlated with histologic grade (p < 0.001), clinical stage (p = 0.04), risk of nodal metastasis (p = 0.02), as well as the likelihood of opting for radical treatment (p = 0.01). Increased expression of miR-21 (p < 0.001) and decreased expression of miR-145 (p < 0.001) were observed in MECs compared to normal salivary gland tissue. MiR-145 negatively (p = 0.01) and miR-21 positively (p = 0.01) correlated with MUC1 overexpression. Based on the univariate cox proportional hazard model, histologic grade and MUC1 expression level were significantly associated with disease-free, cancer-specific, and overall survival. However, the multivariable cox proportional hazard model indicated tumor grade as the only prognostic factor associated with disease-free survival.

Conclusion: Our results support the tumor suppressor role of miR-145 and the oncogenic role of miR-21 in salivary gland MEC. Also, MUC1 and miR-145 overexpression, as well as miR-21 suppression, show promising association with histologic tumor grade and clinical stage.

Keywords: miR-145; miR-21; mucin 1; mucoepidermoid carcinoma; salivary gland neoplasms.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Representative hematoxylin-eosin (H&E) (A, C, E, G) and immunohistochemistry for MUC1 (B, D, F, H) in normal salivary gland tissue (A, B), grade I (C, D), grade II (E, F), and grade III (G, H) MECs
Fig. 2
Fig. 2
Relative expression levels of (A) miR-145 and (B) miR-21. Middle point: median; box: interquartile range (25th to 75th percentiles); whisker: range (excluding outliers). Each error bar is constructed using a 95% confidence interval of the mean
Fig. 3
Fig. 3
Kaplan-Meier curves of overall survival stratified with (A) tumor stage (P = 0.003), (D) grade (P < 0.001), and (G) MUC1 expression level (Low expression (IRS: 0 to 4) vs. high expression (IRS > 4)) (P = 0.04). Kaplan-Meier curves of cancer-specific survival stratified with (B) tumor stage (P = 0.004), (E) grade (P < 0.001), and (H) MUC1 expression level (Low expression (IRS: 0 to 4) vs. high expression (IRS > 4)) (P = 0.04). Kaplan-Meier curves of disease-free survival stratified with (C) tumor stage (P = 0.16), (F) grade (P < 0.001), and (I) MUC1 expression level (Low expression (IRS: 0 to 4) vs. high expression (IRS > 4)) (P = 0.01). Note: P-values are obtained using log-rank test
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