The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity
Background: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with antica...
| Main Authors: | , , , , , , , , |
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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 Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.977025/full |
| _version_ | 1811284144742727680 |
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| author | Lin Cheng Bangbi Weng Changsheng Jia Lin Zhang Bin Hu Li Deng Nan Mou Fengjun Sun Jing Hu |
| author_facet | Lin Cheng Bangbi Weng Changsheng Jia Lin Zhang Bin Hu Li Deng Nan Mou Fengjun Sun Jing Hu |
| author_sort | Lin Cheng |
| collection | DOAJ |
| description | Background: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers.Methods: We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data.Results: There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs.Conclusion: The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy. |
| first_indexed | 2024-04-13T02:24:13Z |
| format | Article |
| id | doaj.art-e61444f2a8894fc99024eab843ec8bc3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T02:24:13Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e61444f2a8894fc99024eab843ec8bc32022-12-22T03:06:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.977025977025The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivityLin ChengBangbi WengChangsheng JiaLin ZhangBin HuLi DengNan MouFengjun SunJing HuBackground: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers.Methods: We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data.Results: There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs.Conclusion: The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy.https://www.frontiersin.org/articles/10.3389/fphar.2022.977025/fullefferocytosisimmune checkpoint-related moleculesimmunotherapychemotherapy resistancecancer |
| spellingShingle | Lin Cheng Bangbi Weng Changsheng Jia Lin Zhang Bin Hu Li Deng Nan Mou Fengjun Sun Jing Hu The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity Frontiers in Pharmacology efferocytosis immune checkpoint-related molecules immunotherapy chemotherapy resistance cancer |
| title | The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| title_full | The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| title_fullStr | The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| title_full_unstemmed | The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| title_short | The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| title_sort | expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity |
| topic | efferocytosis immune checkpoint-related molecules immunotherapy chemotherapy resistance cancer |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.977025/full |
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