Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma
Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRN...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Bioengineered |
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| Online Access: | http://dx.doi.org/10.1080/21655979.2021.1890399 |
| _version_ | 1798034151291486208 |
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| author | Rui Zhang Wei-Jia Mo Lan-Shan Huang Ji-Tian Chen Wei-Zi Wu Wei-Ying He Zhen-Bo Feng |
| author_facet | Rui Zhang Wei-Jia Mo Lan-Shan Huang Ji-Tian Chen Wei-Zi Wu Wei-Ying He Zhen-Bo Feng |
| author_sort | Rui Zhang |
| collection | DOAJ |
| description | Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619–0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways. |
| first_indexed | 2024-04-11T20:40:15Z |
| format | Article |
| id | doaj.art-ef4e57add2e447abb2110b69af88e458 |
| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-11T20:40:15Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Bioengineered |
| spelling | doaj.art-ef4e57add2e447abb2110b69af88e4582022-12-22T04:04:14ZengTaylor & Francis GroupBioengineered2165-59792165-59872021-01-0112185587410.1080/21655979.2021.18903991890399Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular CarcinomaRui Zhang0Wei-Jia Mo1Lan-Shan Huang2Ji-Tian Chen3Wei-Zi Wu4Wei-Ying He5Zhen-Bo Feng6First Affiliated Hospital of Guangxi Medical UniversityFirst Affiliated Hospital of Guangxi Medical UniversityFirst Affiliated Hospital of Guangxi Medical UniversityPeople’s Hospital of Ling ShanPeople’s Hospital of Ling ShanFirst Affiliated Hospital of Guangxi Medical UniversityFirst Affiliated Hospital of Guangxi Medical UniversitySynaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619–0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways.http://dx.doi.org/10.1080/21655979.2021.1890399synaptojanin 2hepatocellular carcinomanomogram predictingdifferentially coexpressed genesmetabolism |
| spellingShingle | Rui Zhang Wei-Jia Mo Lan-Shan Huang Ji-Tian Chen Wei-Zi Wu Wei-Ying He Zhen-Bo Feng Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma Bioengineered synaptojanin 2 hepatocellular carcinoma nomogram predicting differentially coexpressed genes metabolism |
| title | Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma |
| title_full | Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma |
| title_fullStr | Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma |
| title_full_unstemmed | Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma |
| title_short | Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma |
| title_sort | identifying the prognostic risk factors of synaptojanin 2 and its underlying perturbations pathways in hepatocellular carcinoma |
| topic | synaptojanin 2 hepatocellular carcinoma nomogram predicting differentially coexpressed genes metabolism |
| url | http://dx.doi.org/10.1080/21655979.2021.1890399 |
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