Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration
Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our u...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.923503/full |
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| author | Ming-Lang Shih Bashir Lawal Bashir Lawal Sheng-Yao Cheng Janet O. Olugbodi Ahmad O Babalghith Ching-Liang Ho Simona Cavalu Gaber El-Saber Batiha Sarah Albogami Saqer S. Alotaibi Jih-Chin Lee Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu |
| author_facet | Ming-Lang Shih Bashir Lawal Bashir Lawal Sheng-Yao Cheng Janet O. Olugbodi Ahmad O Babalghith Ching-Liang Ho Simona Cavalu Gaber El-Saber Batiha Sarah Albogami Saqer S. Alotaibi Jih-Chin Lee Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu |
| author_sort | Ming-Lang Shih |
| collection | DOAJ |
| description | Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development. |
| first_indexed | 2024-04-12T07:59:30Z |
| format | Article |
| id | doaj.art-132447e514394794a600acae034c298a |
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| language | English |
| last_indexed | 2024-04-12T07:59:30Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-132447e514394794a600acae034c298a2022-12-22T03:41:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.923503923503Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy explorationMing-Lang Shih0Bashir Lawal1Bashir Lawal2Sheng-Yao Cheng3Janet O. Olugbodi4Ahmad O Babalghith5Ching-Liang Ho6Simona Cavalu7Gaber El-Saber Batiha8Sarah Albogami9Saqer S. Alotaibi10Jih-Chin Lee11Alexander T. H. Wu12Alexander T. H. Wu13Alexander T. H. Wu14Alexander T. H. Wu15Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, TaiwanGraduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Biochemistry, Bingham University, Karu, NigeriaMedical Genetics Department, Faculty of Medicine, Umm al-Qura Univeristy, Mecca, Saudi ArabiaDivision of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanFaculty of Medicine and Pharmacy, University of Oradea, Oradea, RomaniaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt0Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia0Department of Biotechnology, College of Science, Taif University, Taif, Saudi ArabiaDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1The PhD Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan2Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan3TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan4Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, TaiwanPapillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.https://www.frontiersin.org/articles/10.3389/fcell.2022.923503/fullthyroid carcinoma (THCA)theranostic biomarkersimmune infiltrationepithelial-to-mesenchymal transitiont-cell exclusion |
| spellingShingle | Ming-Lang Shih Bashir Lawal Bashir Lawal Sheng-Yao Cheng Janet O. Olugbodi Ahmad O Babalghith Ching-Liang Ho Simona Cavalu Gaber El-Saber Batiha Sarah Albogami Saqer S. Alotaibi Jih-Chin Lee Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu Alexander T. H. Wu Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration Frontiers in Cell and Developmental Biology thyroid carcinoma (THCA) theranostic biomarkers immune infiltration epithelial-to-mesenchymal transition t-cell exclusion |
| title | Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| title_full | Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| title_fullStr | Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| title_full_unstemmed | Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| title_short | Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| title_sort | large scale transcriptomic analysis of coding and non coding pathological biomarkers associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration |
| topic | thyroid carcinoma (THCA) theranostic biomarkers immune infiltration epithelial-to-mesenchymal transition t-cell exclusion |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.923503/full |
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