Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients
Background: Non-functional pituitary adenoma (NFPA) is a common tumor that occurs in the pituitary gland, and generally without any symptoms at its early stage and without clinical elevation of hormones, which is commonly diagnosed when it grows up to compress its surrounding tissues and organs. Cur...
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| Format: | Article |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00854/full |
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| author | Tingting Cheng Tingting Cheng Tingting Cheng Ya Wang Ya Wang Ya Wang Miaolong Lu Miaolong Lu Miaolong Lu Xiaohan Zhan Xiaohan Zhan Xiaohan Zhan Tian Zhou Tian Zhou Tian Zhou Biao Li Biao Li Biao Li Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan |
| author_facet | Tingting Cheng Tingting Cheng Tingting Cheng Ya Wang Ya Wang Ya Wang Miaolong Lu Miaolong Lu Miaolong Lu Xiaohan Zhan Xiaohan Zhan Xiaohan Zhan Tian Zhou Tian Zhou Tian Zhou Biao Li Biao Li Biao Li Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan |
| author_sort | Tingting Cheng |
| collection | DOAJ |
| description | Background: Non-functional pituitary adenoma (NFPA) is a common tumor that occurs in the pituitary gland, and generally without any symptoms at its early stage and without clinical elevation of hormones, which is commonly diagnosed when it grows up to compress its surrounding tissues and organs. Currently, the pathogenesis of NFPA has not been clarified yet. It is necessary to investigate molecular alterations in NFPA, and identify reliable biomarkers and drug therapeutic targets for effective treatments.Methods: Tandem mass tags (TMT)-based quantitative proteomics was used to identify and quantify proteins in NFPAs. GO and KEGG enrichment analyses were used to analyze the identified proteins. Differentially expressed genes (DEGs) between NFPA and control tissues were obtained from GEO datasets. These two sets of protein and gene data were analyzed to obtain overlapped molecules (genes; proteins), followed by further GO and KEGG pathway analyses of these overlapped molecules, and molecular network analysis to obtain the hub molecules with Cytoscape. Two hub molecules (SRC and AKT1) were verified with Western blotting.Results: Totally 6076 proteins in NFPA tissues were identified, and 3598 DEGs between NFPA and control tissues were identified from GEO database. Overlapping analysis of 6076 proteins and 3598 DEGs obtained 1088 overlapped molecules (DEGs; proteins). KEGG pathway analysis of 6076 proteins obtained 114 statistically significant pathways, including endocytosis, and spliceosome signaling pathways. KEGG pathway analysis of 1088 overlapped molecules obtained 52 statistically significant pathways, including focal adhesion, cGMP-PKG pathway, and platelet activation signaling pathways. These pathways play important roles in cell energy supply, adhesion, and maintenance of the tumor microenvironment. According to the association degree in Cytoscape, ten hub molecules (DEGs; proteins) were identified, including GAPDH, ALB, ACACA, SRC, ENO2, CALM1, POTEE, HSPA8, DECR1, and AKT1. Western-blotting analysis confirmed the upregulated expressions of SRC and PTMScan experiment confirmed the increased levels of pAKT1, in NFPAs compared to controls.Conclusions: This study established the large-scale quantitative protein profiling of NFPA tissue proteome. It offers a basis for subsequent in-depth proteomics analysis of NFPAs, and insight into the molecular mechanism of NFPAs. It also provided the basic data to discover reliable biomarkers and therapeutic targets for NFPA patients. |
| first_indexed | 2024-12-11T21:08:35Z |
| format | Article |
| id | doaj.art-341a6bd5ce5e4ce78834aa5c47ee7a97 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T21:08:35Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-341a6bd5ce5e4ce78834aa5c47ee7a972022-12-22T00:50:48ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-12-011010.3389/fendo.2019.00854428514Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the PatientsTingting Cheng0Tingting Cheng1Tingting Cheng2Ya Wang3Ya Wang4Ya Wang5Miaolong Lu6Miaolong Lu7Miaolong Lu8Xiaohan Zhan9Xiaohan Zhan10Xiaohan Zhan11Tian Zhou12Tian Zhou13Tian Zhou14Biao Li15Biao Li16Biao Li17Xianquan Zhan18Xianquan Zhan19Xianquan Zhan20Xianquan Zhan21Xianquan Zhan22Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, Changsha, ChinaState Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaBackground: Non-functional pituitary adenoma (NFPA) is a common tumor that occurs in the pituitary gland, and generally without any symptoms at its early stage and without clinical elevation of hormones, which is commonly diagnosed when it grows up to compress its surrounding tissues and organs. Currently, the pathogenesis of NFPA has not been clarified yet. It is necessary to investigate molecular alterations in NFPA, and identify reliable biomarkers and drug therapeutic targets for effective treatments.Methods: Tandem mass tags (TMT)-based quantitative proteomics was used to identify and quantify proteins in NFPAs. GO and KEGG enrichment analyses were used to analyze the identified proteins. Differentially expressed genes (DEGs) between NFPA and control tissues were obtained from GEO datasets. These two sets of protein and gene data were analyzed to obtain overlapped molecules (genes; proteins), followed by further GO and KEGG pathway analyses of these overlapped molecules, and molecular network analysis to obtain the hub molecules with Cytoscape. Two hub molecules (SRC and AKT1) were verified with Western blotting.Results: Totally 6076 proteins in NFPA tissues were identified, and 3598 DEGs between NFPA and control tissues were identified from GEO database. Overlapping analysis of 6076 proteins and 3598 DEGs obtained 1088 overlapped molecules (DEGs; proteins). KEGG pathway analysis of 6076 proteins obtained 114 statistically significant pathways, including endocytosis, and spliceosome signaling pathways. KEGG pathway analysis of 1088 overlapped molecules obtained 52 statistically significant pathways, including focal adhesion, cGMP-PKG pathway, and platelet activation signaling pathways. These pathways play important roles in cell energy supply, adhesion, and maintenance of the tumor microenvironment. According to the association degree in Cytoscape, ten hub molecules (DEGs; proteins) were identified, including GAPDH, ALB, ACACA, SRC, ENO2, CALM1, POTEE, HSPA8, DECR1, and AKT1. Western-blotting analysis confirmed the upregulated expressions of SRC and PTMScan experiment confirmed the increased levels of pAKT1, in NFPAs compared to controls.Conclusions: This study established the large-scale quantitative protein profiling of NFPA tissue proteome. It offers a basis for subsequent in-depth proteomics analysis of NFPAs, and insight into the molecular mechanism of NFPAs. It also provided the basic data to discover reliable biomarkers and therapeutic targets for NFPA patients.https://www.frontiersin.org/article/10.3389/fendo.2019.00854/fullnon-functional pituitary adenomasquantitative proteomicsmolecular networkTranscriptomicsIntegrative analysis of proteomics and transcriptomicssignaling pathway |
| spellingShingle | Tingting Cheng Tingting Cheng Tingting Cheng Ya Wang Ya Wang Ya Wang Miaolong Lu Miaolong Lu Miaolong Lu Xiaohan Zhan Xiaohan Zhan Xiaohan Zhan Tian Zhou Tian Zhou Tian Zhou Biao Li Biao Li Biao Li Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan Xianquan Zhan Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients Frontiers in Endocrinology non-functional pituitary adenomas quantitative proteomics molecular network Transcriptomics Integrative analysis of proteomics and transcriptomics signaling pathway |
| title | Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients |
| title_full | Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients |
| title_fullStr | Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients |
| title_full_unstemmed | Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients |
| title_short | Quantitative Analysis of Proteome in Non-functional Pituitary Adenomas: Clinical Relevance and Potential Benefits for the Patients |
| title_sort | quantitative analysis of proteome in non functional pituitary adenomas clinical relevance and potential benefits for the patients |
| topic | non-functional pituitary adenomas quantitative proteomics molecular network Transcriptomics Integrative analysis of proteomics and transcriptomics signaling pathway |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00854/full |
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