MiR-221, miR-320a, miR133a, and miR-133b as potential biomarkers in leiomyosarcoma

Background: Leiomyosarcoma is an aggressive tumor with a high rate of distant metastasis and poor prognosis. No standardized biomarkers are available to assess early diagnosis or monitoring during the clinical course. MicroRNAs (miRNAs) function in modulating a multitude of targets and are involved in tumorigenesis, cancer progression, and metastasis. This study was designed to evaluate miR-221, miR-320a, miR-133a, and miR-133b as potential biomarkers in leiomyosarcoma. Materials and methods: The expression levels of miR-221, miR-320a, miR-133a, and miR-133b as well as their target mRNAs CDKN1B , TGFBR1 , and IGF1R were assessed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in tissue samples from 33 patients with leiomyosarcoma. Wilcoxon test, Kruskal-Wallis test, Mann-Whitney test as well as Spearman-Rho-test were used for statistical analysis. Receiver operating characteristic (ROC) analyses were performed to discriminate metastatic risk of local and primary tumors in correlation to miR-221, miR-320a, miR-133a, and miR-133b. Results: and discussion The expression levels of miR-221, miR-320a, and miR-133a were significantly upregulated in leiomyosarcoma tumor tissue compared to adjacent non-tumor tissue (p = 0.003 for miR-221, p = 0.006 for miR-320a, and p = 0.044 for miR-133a respectively). The target mRNAs CDKN1B , TGFBR1 , and IGF1R in 25 leiomyosarcoma tumor tissues were not significantly deregulated. There was no significant upregulation in primary tumors and metastases compared to local tumors for miR-221, miR-320a, miR-133a, and miR-133b. ROC curves of miRNA-221, miR-320a, miR-133a, and miR-133b to predict metastatic risk at initial presentation of the tumor, comparing non-metastasizing and metastasizing leiomyosarcomas, demonstrated no significant levels. Conclusion: miR-221, miR-320a, and miR-133a were significantly upregulated in leiomyosarcoma tumor tissue as compared to adjacent non-tumor tissue. There was no significant difference in miRNA expression and ROC curves in primary tumors as compared to local tumors. While not statistically significant, ROC curve of miR-133b suggests a potential role in predicting metastatic risk, warranting subsequent analysis. This study provides evidence for further evaluation of miR-221, miR-320a, miR-133a, and miR-133b as biomarkers in primary diagnosis and assessment of metastatic risk in leiomyosarcoma.