Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer
Abstract Emerging evidence has indicated that m5C modification plays a vital role in cancer development. However, the function of m5C-lncRNAs in PTC has never been reported. This study aims to explore the regulation mechanism of m5C RNA methylation-related long noncoding RNAs (m5C-lncRNAs) in papill...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-88657-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823862164907098112 |
|---|---|
| author | Ying Ding Xinying Li Wenlong Wang Lei Cai |
| author_facet | Ying Ding Xinying Li Wenlong Wang Lei Cai |
| author_sort | Ying Ding |
| collection | DOAJ |
| description | Abstract Emerging evidence has indicated that m5C modification plays a vital role in cancer development. However, the function of m5C-lncRNAs in PTC has never been reported. This study aims to explore the regulation mechanism of m5C RNA methylation-related long noncoding RNAs (m5C-lncRNAs) in papillary thyroid cancer (PTC). Bioinformatics analysis was used to investigate the role of m5C-lncRNAs in the prognosis and tumor immune microenvironment of PTC. Subsequently, we preliminarily verified the regulation mechanisms of m5C-lncRNAs in vivo and in vitro experiments. A total of six m5C-lncRNAs and five immune cell types were selected to construct the risk score and immune risk score (IRS) model, respectively. Patients with a high-risk score had a worse prognosis and the ROC indicated a reliable prediction performance (AUC = 0.796). As expected, the ESTIMATE and immune scores were higher (P < 0.001) and the tumor purity (P < 0.05) was significantly lower in the low-risk subgroup. CIBERSORT analysis showed Tregs, M0 macrophages, dendritic cells resting, and eosinophils were positively correlated to the risk score. Moreover, the expression levels of PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, and KLRB1 were lower in the high-risk subgroup. Importantly, patients in high-risk subgroup tended to have a better response to immunotherapy than those in low-risk subgroup (P = 0.022). Similar to the above risk score, the IRS model also showed favorable prognosis predictive performance (AUC = 0.764). An integrated nomogram combining risk score, IRS, and age exhibited good prognostic predictive performance. Additionally, we validate the downregulation of PPP1R12A-AS1 promotes proliferation and metastasis by activating the MAPK signaling pathway. Our research confirms that m5C-lncRNAs not only contribute to evaluating the prognosis of patients with PTC but also help predict immune cell infiltration and immunotherapy response. |
| format | Article |
| id | doaj-art-5464278e2bd84dbfbf7dcfc51b2a4077 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5464278e2bd84dbfbf7dcfc51b2a40772025-02-09T12:37:09ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-88657-2Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancerYing Ding0Xinying Li1Wenlong Wang2Lei Cai3Department of Breast Thyroid Surgery, Third Xiangya Hospital, Central South UniversityDepartment of Thyroid Surgery, Xiangya Hospital, Central South UniversityDepartment of Breast Surgery, Xiangya Hospital, Central South UniversityDepartment of Breast Thyroid Surgery, Third Xiangya Hospital, Central South UniversityAbstract Emerging evidence has indicated that m5C modification plays a vital role in cancer development. However, the function of m5C-lncRNAs in PTC has never been reported. This study aims to explore the regulation mechanism of m5C RNA methylation-related long noncoding RNAs (m5C-lncRNAs) in papillary thyroid cancer (PTC). Bioinformatics analysis was used to investigate the role of m5C-lncRNAs in the prognosis and tumor immune microenvironment of PTC. Subsequently, we preliminarily verified the regulation mechanisms of m5C-lncRNAs in vivo and in vitro experiments. A total of six m5C-lncRNAs and five immune cell types were selected to construct the risk score and immune risk score (IRS) model, respectively. Patients with a high-risk score had a worse prognosis and the ROC indicated a reliable prediction performance (AUC = 0.796). As expected, the ESTIMATE and immune scores were higher (P < 0.001) and the tumor purity (P < 0.05) was significantly lower in the low-risk subgroup. CIBERSORT analysis showed Tregs, M0 macrophages, dendritic cells resting, and eosinophils were positively correlated to the risk score. Moreover, the expression levels of PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, and KLRB1 were lower in the high-risk subgroup. Importantly, patients in high-risk subgroup tended to have a better response to immunotherapy than those in low-risk subgroup (P = 0.022). Similar to the above risk score, the IRS model also showed favorable prognosis predictive performance (AUC = 0.764). An integrated nomogram combining risk score, IRS, and age exhibited good prognostic predictive performance. Additionally, we validate the downregulation of PPP1R12A-AS1 promotes proliferation and metastasis by activating the MAPK signaling pathway. Our research confirms that m5C-lncRNAs not only contribute to evaluating the prognosis of patients with PTC but also help predict immune cell infiltration and immunotherapy response.https://doi.org/10.1038/s41598-025-88657-2Papillary thyroid cancer (PTC)Tumor microenvironmentPrognosis5-methylcytosine (m5C)NomogramImmunotherapy |
| spellingShingle | Ying Ding Xinying Li Wenlong Wang Lei Cai Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer Scientific Reports Papillary thyroid cancer (PTC) Tumor microenvironment Prognosis 5-methylcytosine (m5C) Nomogram Immunotherapy |
| title | Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer |
| title_full | Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer |
| title_fullStr | Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer |
| title_full_unstemmed | Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer |
| title_short | Integrative analysis of 5-methylcytosine associated signature in papillary thyroid cancer |
| title_sort | integrative analysis of 5 methylcytosine associated signature in papillary thyroid cancer |
| topic | Papillary thyroid cancer (PTC) Tumor microenvironment Prognosis 5-methylcytosine (m5C) Nomogram Immunotherapy |
| url | https://doi.org/10.1038/s41598-025-88657-2 |
| work_keys_str_mv | AT yingding integrativeanalysisof5methylcytosineassociatedsignatureinpapillarythyroidcancer AT xinyingli integrativeanalysisof5methylcytosineassociatedsignatureinpapillarythyroidcancer AT wenlongwang integrativeanalysisof5methylcytosineassociatedsignatureinpapillarythyroidcancer AT leicai integrativeanalysisof5methylcytosineassociatedsignatureinpapillarythyroidcancer |