Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer
Background: The incidence of thyroid cancer in women is 3–4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. Methods: Ingenuity pathways analysis was used to define sex...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/7/1260 |
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| author | Leila Shobab Hui Zheng Kirk Jensen Maria Cecilia Mendonca-Torres Matthew McCoy Victoria Hoperia Jennifer Rosen Leonard Wartofsky Kenneth Burman Vasyl Vasko |
| author_facet | Leila Shobab Hui Zheng Kirk Jensen Maria Cecilia Mendonca-Torres Matthew McCoy Victoria Hoperia Jennifer Rosen Leonard Wartofsky Kenneth Burman Vasyl Vasko |
| author_sort | Leila Shobab |
| collection | DOAJ |
| description | Background: The incidence of thyroid cancer in women is 3–4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. Methods: Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. Results: In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. Conclusions: Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis. |
| first_indexed | 2024-04-24T10:49:28Z |
| format | Article |
| id | doaj.art-f782d888d9324b1c92ef511dc9eaf859 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-24T10:49:28Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f782d888d9324b1c92ef511dc9eaf8592024-04-12T13:15:52ZengMDPI AGCancers2072-66942024-03-01167126010.3390/cancers16071260Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid CancerLeila Shobab0Hui Zheng1Kirk Jensen2Maria Cecilia Mendonca-Torres3Matthew McCoy4Victoria Hoperia5Jennifer Rosen6Leonard Wartofsky7Kenneth Burman8Vasyl Vasko9Department of Medicine, Division of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, USADepartment of Surgery, MedStar Washington Hospital Center, Washington, DC 20010, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USAInnovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC 20007, USAInstitute of Biology and Medicine, Kyiv National University, 02000 Kyiv, UkraineDepartment of Surgery, MedStar Washington Hospital Center, Washington, DC 20010, USADepartment of Medicine, Division of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, USADepartment of Medicine, Division of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, USADepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USABackground: The incidence of thyroid cancer in women is 3–4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. Methods: Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. Results: In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. Conclusions: Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis.https://www.mdpi.com/2072-6694/16/7/1260thyroid cancersex differenceKDMshistone lysine demethylases |
| spellingShingle | Leila Shobab Hui Zheng Kirk Jensen Maria Cecilia Mendonca-Torres Matthew McCoy Victoria Hoperia Jennifer Rosen Leonard Wartofsky Kenneth Burman Vasyl Vasko Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer Cancers thyroid cancer sex difference KDMs histone lysine demethylases |
| title | Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer |
| title_full | Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer |
| title_fullStr | Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer |
| title_full_unstemmed | Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer |
| title_short | Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer |
| title_sort | sex specific expression of histone lysine demethylases kdms in thyroid cancer |
| topic | thyroid cancer sex difference KDMs histone lysine demethylases |
| url | https://www.mdpi.com/2072-6694/16/7/1260 |
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