ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer
Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is h...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-02-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024008867 |
| _version_ | 1827348419649208320 |
|---|---|
| author | Yiyuan Liu Jinyao Wu Lingzhi Chen Juan Zou Qiuping Yang Huiting Tian Daitian Zheng Zeqi Ji Jiehui Cai Zhiyang Li Yexi Chen |
| author_facet | Yiyuan Liu Jinyao Wu Lingzhi Chen Juan Zou Qiuping Yang Huiting Tian Daitian Zheng Zeqi Ji Jiehui Cai Zhiyang Li Yexi Chen |
| author_sort | Yiyuan Liu |
| collection | DOAJ |
| description | Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer. |
| first_indexed | 2024-03-08T00:11:58Z |
| format | Article |
| id | doaj.art-4300a4c8dcc74ffb99f9daf8d8ac248e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T00:11:58Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4300a4c8dcc74ffb99f9daf8d8ac248e2024-02-17T06:38:52ZengElsevierHeliyon2405-84402024-02-01103e24855ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancerYiyuan Liu0Jinyao Wu1Lingzhi Chen2Juan Zou3Qiuping Yang4Huiting Tian5Daitian Zheng6Zeqi Ji7Jiehui Cai8Zhiyang Li9Yexi Chen10Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaCorresponding author. No.69 North Dongxia Road, Shantou, Guangdong, 515041, China.; Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaCorresponding author. No.69 North Dongxia Road, Shantou, Guangdong, 515041, China.; Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaBreast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.http://www.sciencedirect.com/science/article/pii/S2405844024008867TET3Breast cancerPrognosis biomarkerceRNATumor immune microenvironmentCancer immunotherapy |
| spellingShingle | Yiyuan Liu Jinyao Wu Lingzhi Chen Juan Zou Qiuping Yang Huiting Tian Daitian Zheng Zeqi Ji Jiehui Cai Zhiyang Li Yexi Chen ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer Heliyon TET3 Breast cancer Prognosis biomarker ceRNA Tumor immune microenvironment Cancer immunotherapy |
| title | ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| title_full | ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| title_fullStr | ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| title_full_unstemmed | ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| title_short | ncRNAs-mediated overexpression of TET3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| title_sort | ncrnas mediated overexpression of tet3 predicts unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer |
| topic | TET3 Breast cancer Prognosis biomarker ceRNA Tumor immune microenvironment Cancer immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024008867 |
| work_keys_str_mv | AT yiyuanliu ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT jinyaowu ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT lingzhichen ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT juanzou ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT qiupingyang ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT huitingtian ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT daitianzheng ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT zeqiji ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT jiehuicai ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT zhiyangli ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer AT yexichen ncrnasmediatedoverexpressionoftet3predictsunfavorableprognosisandcorrelateswithimmunotherapyefficacyinbreastcancer |