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Phosphorylated Mechanistic Target of Rapamycin (p-mTOR) and Noncoding RNA Expression in Follicular and Hürthle Cell
Adam Covach1, Sanjay Patel1, Heather Hardin1
1Department of Pathology and Laboratory Medicine, University of Wisconsin, School of Medicine and Public Health, 600 Highland Ave, Box 8550, Madison, WI, 53792, USA.
Abstract:
Oncocytic (Hürthle cell) and follicular neoplasms are related thyroid tumors with distinct molecular profiles. Diagnostic criteria separating adenomas and carcinomas for these two types of neoplasms are similar, but there may be some differences in the biological behavior of Hürthle cell and follicular carcinomas. Recent studies have shown that noncoding RNAs may have diagnostic and prognostic utility in separating benign and malignant Hürthle cell and follicular neoplasms. In this study, we examined expression of various noncoding RNAs including metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and miR-RNA-885-5p (miR-885) in distinguishing between benign and malignant neoplasms. In addition, the expression of phosphorylated mechanistic receptor of rapamycin (p-mTOR) was also analyzed in these two groups of tumors. Tissue microarrays (TMAs) with archived tissue samples were analyzed using in situ hybridization (ISH) for MALAT1 and miR-885 and immunohistochemistry (IHC) for p-mTOR. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was also performed on a subset of the cases.MALAT1 and miR-885 were increased in all neoplastic groups compared to the normal thyroid tissues (p < 0.05). MALAT1 was more highly expressed in HCCs compared to FTCs, although the differences were not statistically significant (p = 0.06). MiR-885 was expressed at similar levels in FTCs and HCCs. P-mTOR protein was more highly expressed in FTCs than in HCCs (p<0.001). qRT-PCR analysis of noncoding RNAs supported the ISH findings. These results indicate that the noncoding RNAs MALAT1 and miR-885 show increased expression in neoplastic follicular and Hürthle cell thyroid neoplasms compared to normal thyroid tissues. P-mTOR was most highly expressed in FTC but was also increased in HCC, suggesting that drugs targeting this pathway may be useful for treatment of tumors unresponsive to conventional therapies.
Insights
Noncoding RNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and miR-RNA-885-5p (miR-885) are elevated in thyroid neoplasms. Phosphorylated mechanistic target of rapamycin (p-mTOR) is highly expressed in follicular thyroid carcinomas, suggesting potential therapeutic targets.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Oncocytic (Hürthle cell) and follicular neoplasms are related thyroid tumors with overlapping diagnostic criteria but potentially different biological behaviors.
- Noncoding RNAs (ncRNAs) are emerging as potential biomarkers for distinguishing benign from malignant thyroid neoplasms.
- Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and miR-RNA-885-5p (miR-885) are ncRNAs of interest in cancer research.
Purpose of the Study:
- To investigate the expression of MALAT1 and miR-885 in distinguishing between benign and malignant Hürthle cell and follicular thyroid neoplasms.
- To analyze the expression of phosphorylated mechanistic target of rapamycin (p-mTOR) in these tumor types.
- To evaluate the diagnostic and prognostic utility of these molecular markers.
Main Methods:
- Tissue microarrays (TMAs) of archived thyroid tumor samples were utilized.
- In situ hybridization (ISH) was performed for MALAT1 and miR-885 expression analysis.
- Immunohistochemistry (IHC) was used to assess p-mTOR protein levels.
- Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was employed for ncRNA analysis.
Main Results:
- Both MALAT1 and miR-885 showed increased expression in neoplastic thyroid tissues compared to normal tissues (p < 0.05).
- MALAT1 expression was higher in Hürthle cell carcinomas (HCCs) than follicular thyroid carcinomas (FTCs), though not statistically significant (p = 0.06).
- MiR-885 expression levels were similar between FTCs and HCCs.
- P-mTOR protein was significantly more highly expressed in FTCs than in HCCs (p < 0.001).
- qRT-PCR results corroborated the ISH findings for ncRNAs.
Conclusions:
- MALAT1 and miR-885 are upregulated in follicular and Hürthle cell thyroid neoplasms, indicating their potential as biomarkers.
- Elevated p-mTOR in FTCs suggests this pathway as a potential therapeutic target for treatment-resistant tumors.
- These molecular markers may aid in the differential diagnosis and management of thyroid neoplasms.
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