A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint
The aim of this study was to evaluate the association between Ferredoxin 1 (FDX1) expression and the prognostic survival of tumor patients and predict the efficacy of immunotherapy response to antitumor drug sensitivity. FDX1 plays an oncogenic role in thirty-three types of tumors, based on TCGA and...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9182 |
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| author | Huijiao Lu Jiahua Liang Xue He Huabin Ye Chuangdong Ruan Hongwei Shao Rongxin Zhang Yan Li |
| author_facet | Huijiao Lu Jiahua Liang Xue He Huabin Ye Chuangdong Ruan Hongwei Shao Rongxin Zhang Yan Li |
| author_sort | Huijiao Lu |
| collection | DOAJ |
| description | The aim of this study was to evaluate the association between Ferredoxin 1 (FDX1) expression and the prognostic survival of tumor patients and predict the efficacy of immunotherapy response to antitumor drug sensitivity. FDX1 plays an oncogenic role in thirty-three types of tumors, based on TCGA and GEO databases, and further experimental validation in vitro was provided through multiple cell lines. FDX1 was expressed highly in multiple types of cancer and differently linked to the survival prognosis of tumorous patients. A high phosphorylation level was correlated with the FDX1 site of S177 in lung cancer. FDX1 exhibited a significant association with infiltrated cancer-associated fibroblasts and CD8<sup>+</sup> T cells. Moreover, FDX1 demonstrated correlations with immune and molecular subtypes, as well as functional enrichments in GO/KEGG pathways. Additionally, FDX1 displayed relationships with the tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and RNA and DNA synthesis (RNAss/DNAss) within the tumor microenvironment. Notably, FDX1 exhibited a strong connection with immune checkpoint genes in the co-expression network. The validity of these findings was further confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on WM115 and A375 tumor cells. Elevated FDX1 expression has been linked to the enhanced effectiveness of PD-L1 blockade immunotherapy in melanoma, as observed in the GSE22155 and GSE172320 cohorts. Autodocking simulations have suggested that FDX1 may influence drug resistance by affecting the binding sites of antitumor drugs. Collectively, these findings propose that FDX1 could serve as a novel and valuable biomarker and represent an immunotherapeutic target for augmenting immune responses in various human cancers when used in combination with immune checkpoint inhibitors. |
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| spelling | doaj.art-81233bd4382a4cddb6f9a471456a6cb12023-11-18T07:55:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411918210.3390/ijms24119182A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune CheckpointHuijiao Lu0Jiahua Liang1Xue He2Huabin Ye3Chuangdong Ruan4Hongwei Shao5Rongxin Zhang6Yan Li7Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaThe aim of this study was to evaluate the association between Ferredoxin 1 (FDX1) expression and the prognostic survival of tumor patients and predict the efficacy of immunotherapy response to antitumor drug sensitivity. FDX1 plays an oncogenic role in thirty-three types of tumors, based on TCGA and GEO databases, and further experimental validation in vitro was provided through multiple cell lines. FDX1 was expressed highly in multiple types of cancer and differently linked to the survival prognosis of tumorous patients. A high phosphorylation level was correlated with the FDX1 site of S177 in lung cancer. FDX1 exhibited a significant association with infiltrated cancer-associated fibroblasts and CD8<sup>+</sup> T cells. Moreover, FDX1 demonstrated correlations with immune and molecular subtypes, as well as functional enrichments in GO/KEGG pathways. Additionally, FDX1 displayed relationships with the tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and RNA and DNA synthesis (RNAss/DNAss) within the tumor microenvironment. Notably, FDX1 exhibited a strong connection with immune checkpoint genes in the co-expression network. The validity of these findings was further confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on WM115 and A375 tumor cells. Elevated FDX1 expression has been linked to the enhanced effectiveness of PD-L1 blockade immunotherapy in melanoma, as observed in the GSE22155 and GSE172320 cohorts. Autodocking simulations have suggested that FDX1 may influence drug resistance by affecting the binding sites of antitumor drugs. Collectively, these findings propose that FDX1 could serve as a novel and valuable biomarker and represent an immunotherapeutic target for augmenting immune responses in various human cancers when used in combination with immune checkpoint inhibitors.https://www.mdpi.com/1422-0067/24/11/9182FDX1tumor immune microenvironment (TME)immune checkpoint genes (ICPs)anti-tumor immunotherapyflow cytometry (FCM)PD-L1 |
| spellingShingle | Huijiao Lu Jiahua Liang Xue He Huabin Ye Chuangdong Ruan Hongwei Shao Rongxin Zhang Yan Li A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint International Journal of Molecular Sciences FDX1 tumor immune microenvironment (TME) immune checkpoint genes (ICPs) anti-tumor immunotherapy flow cytometry (FCM) PD-L1 |
| title | A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint |
| title_full | A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint |
| title_fullStr | A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint |
| title_full_unstemmed | A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint |
| title_short | A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint |
| title_sort | novel oncogenic role of fdx1 in human melanoma related to pd l1 immune checkpoint |
| topic | FDX1 tumor immune microenvironment (TME) immune checkpoint genes (ICPs) anti-tumor immunotherapy flow cytometry (FCM) PD-L1 |
| url | https://www.mdpi.com/1422-0067/24/11/9182 |
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