Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors
The primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovaria...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.943006/full |
| _version_ | 1811286251173576704 |
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| author | Qiuju Liang Qiuju Liang Jinwu Peng Jinwu Peng Zhijie Xu Zhilan Li Feng Jiang Lingzi Ouyang Shangjun Wu Chencheng Fu Ying Liu Yuanhong Liu Yuanhong Liu Yuanliang Yan Yuanliang Yan |
| author_facet | Qiuju Liang Qiuju Liang Jinwu Peng Jinwu Peng Zhijie Xu Zhilan Li Feng Jiang Lingzi Ouyang Shangjun Wu Chencheng Fu Ying Liu Yuanhong Liu Yuanhong Liu Yuanliang Yan Yuanliang Yan |
| author_sort | Qiuju Liang |
| collection | DOAJ |
| description | The primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovarian cancer, glioma, and non-small-cell lung carcinoma, respectively, were collected for the screening process, and two genes were found. A-kinase anchor protein 12 (AKAP12), one of these two genes, correlates with tumorigenesis of some cancers. However, the role of AKAP12 in pan-cancer remains poorly defined. The present study first systematically analyzed the association of AKAP12 with anti-VEGF inhibitors’ sensitivity, clinical prognosis, DNA methylation, protein phosphorylation, and immune cell infiltration across various cancers via bioinformatic tools. We found that AKAP12 was upregulated in anti-VEGF therapy-resistant cancers, including ovarian cancer (OV), glioblastoma (GBM), lung cancer, and colorectal cancer (CRC). A high AKAP12 expression revealed dismal prognoses in OV, GBM, and CRC patients receiving anti-VEGF inhibitors. Moreover, AKAP12 expression was negatively correlated with cancer sensitivity towards anti-VEGF therapy. Clinical prognosis analysis showed that AKAP12 expression predicted worse prognoses of various cancer types encompassing colon adenocarcinoma (COAD), OV, GBM, and lung squamous cell carcinoma (LUSC). Gene mutation status may be a critical cause for the involvement of AKAP12 in resistance. Furthermore, lower expression of AKAP12 was detected in nearly all cancer types, and hypermethylation may explain its decreased expression. A decreased phosphorylation of T1760 was observed in breast cancer, clear-cell renal cell carcinoma, and lung adenocarcinoma. For the immunologic significance, AKAP12 was positively related to the abundance of pro-tumor cancer-associated fibroblasts (CAFs) in various types of cancer. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that “cell junction organization” and “MAPK pathway” participated in the effect of AKAP12. Importantly, we discovered that AKAP12 expression was greatly associated with metastasis of lung adenocarcinoma as well as differential and angiogenesis of retinoblastoma through investigating the single-cell sequencing data. Our study showed that the dual role of AKAP12 in various cancers and AKAP12 could serve as a biomarker of anti-VEGF resistance in OV, GBM, LUSC, and COAD. |
| first_indexed | 2024-04-13T02:55:57Z |
| format | Article |
| id | doaj.art-711063027e894eb5a1c9cc43195daedc |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T02:55:57Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-711063027e894eb5a1c9cc43195daedc2022-12-22T03:05:38ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.943006943006Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitorsQiuju Liang0Qiuju Liang1Jinwu Peng2Jinwu Peng3Zhijie Xu4Zhilan Li5Feng Jiang6Lingzi Ouyang7Shangjun Wu8Chencheng Fu9Ying Liu10Yuanhong Liu11Yuanhong Liu12Yuanliang Yan13Yuanliang Yan14Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Institute for Rational and Safe Medication Practices, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pathology, Xiangya Changde Hospital, Changde, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Institute for Rational and Safe Medication Practices, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Institute for Rational and Safe Medication Practices, Xiangya Hospital, Central South University, Changsha, ChinaThe primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovarian cancer, glioma, and non-small-cell lung carcinoma, respectively, were collected for the screening process, and two genes were found. A-kinase anchor protein 12 (AKAP12), one of these two genes, correlates with tumorigenesis of some cancers. However, the role of AKAP12 in pan-cancer remains poorly defined. The present study first systematically analyzed the association of AKAP12 with anti-VEGF inhibitors’ sensitivity, clinical prognosis, DNA methylation, protein phosphorylation, and immune cell infiltration across various cancers via bioinformatic tools. We found that AKAP12 was upregulated in anti-VEGF therapy-resistant cancers, including ovarian cancer (OV), glioblastoma (GBM), lung cancer, and colorectal cancer (CRC). A high AKAP12 expression revealed dismal prognoses in OV, GBM, and CRC patients receiving anti-VEGF inhibitors. Moreover, AKAP12 expression was negatively correlated with cancer sensitivity towards anti-VEGF therapy. Clinical prognosis analysis showed that AKAP12 expression predicted worse prognoses of various cancer types encompassing colon adenocarcinoma (COAD), OV, GBM, and lung squamous cell carcinoma (LUSC). Gene mutation status may be a critical cause for the involvement of AKAP12 in resistance. Furthermore, lower expression of AKAP12 was detected in nearly all cancer types, and hypermethylation may explain its decreased expression. A decreased phosphorylation of T1760 was observed in breast cancer, clear-cell renal cell carcinoma, and lung adenocarcinoma. For the immunologic significance, AKAP12 was positively related to the abundance of pro-tumor cancer-associated fibroblasts (CAFs) in various types of cancer. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that “cell junction organization” and “MAPK pathway” participated in the effect of AKAP12. Importantly, we discovered that AKAP12 expression was greatly associated with metastasis of lung adenocarcinoma as well as differential and angiogenesis of retinoblastoma through investigating the single-cell sequencing data. Our study showed that the dual role of AKAP12 in various cancers and AKAP12 could serve as a biomarker of anti-VEGF resistance in OV, GBM, LUSC, and COAD.https://www.frontiersin.org/articles/10.3389/fgene.2022.943006/fullresistanceAKAP12pan-cancer analysisimmune infiltrationprognosis |
| spellingShingle | Qiuju Liang Qiuju Liang Jinwu Peng Jinwu Peng Zhijie Xu Zhilan Li Feng Jiang Lingzi Ouyang Shangjun Wu Chencheng Fu Ying Liu Yuanhong Liu Yuanhong Liu Yuanliang Yan Yuanliang Yan Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors Frontiers in Genetics resistance AKAP12 pan-cancer analysis immune infiltration prognosis |
| title | Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors |
| title_full | Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors |
| title_fullStr | Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors |
| title_full_unstemmed | Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors |
| title_short | Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors |
| title_sort | pan cancer analysis of the prognosis and immunological role of akap12 a potential biomarker for resistance to anti vegf inhibitors |
| topic | resistance AKAP12 pan-cancer analysis immune infiltration prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.943006/full |
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