DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer
Ovarian carcinoma (OV) is a lethal gynecological malignancy. Most OV patients develop resistance to platinum-based chemotherapy and recurrence. Peroxisome proliferator-activated receptors (PPARs) are the ligand activating transcription factor of the nuclear receptor superfamily. PPARs as important t...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6629842 |
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| author | Qianqian Zhao Jie Zhong Ping Lu Xiao Feng Ying Han Chenqi Ling Wenke Guo Weijin Zhou Fudong Yu |
| author_facet | Qianqian Zhao Jie Zhong Ping Lu Xiao Feng Ying Han Chenqi Ling Wenke Guo Weijin Zhou Fudong Yu |
| author_sort | Qianqian Zhao |
| collection | DOAJ |
| description | Ovarian carcinoma (OV) is a lethal gynecological malignancy. Most OV patients develop resistance to platinum-based chemotherapy and recurrence. Peroxisome proliferator-activated receptors (PPARs) are the ligand activating transcription factor of the nuclear receptor superfamily. PPARs as important transcriptional regulators regulate important physiological processes such as lipid metabolism, inflammation, and wound healing. Several reports point out that PPARs can also have an effect on the sensitivity of tumor cells to platinum-based chemotherapy drugs. However, the role of PPAR-target related genes (PPAR-TRGs) in chemotherapeutic resistance of OV remains unclear. The present study is aimed at optimizing candidate genes by integrating platinum-chemotherapy expression data and PPAR family genes with their targets. The gene expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. A total of 4 genes (AP2A2, DOCK4, HSDL2, and PDK4) were the candidate differentially expressed genes (DEGs) of PPAR-TRGs with platinum chemosensitivity. After conducting numerous survival analyses using different cohorts, we found that only the upexpression of DOCK4 has important significance with the poor prognosis of OV patients. Meanwhile, DOCK4 is detected in plasma and enriched in neutrophil and monocyte cells of the blood. We further found that there were significant correlations between DOCK4 expression and the levels of CD4+ T cell infiltration, dendritic cell infiltration, and neutrophil infiltration in OV. In addition, we verified the expression level of DOCK4 in OV cell lines treated with platinum drugs and found that DOCK4 is potentially responsive to platinum drugs. In conclusion, DOCK4 is potentially associated with immune cell infiltration and represents a valuable prognostic biomarker in ovarian cancer patients. |
| format | Article |
| id | doaj-art-f2a05f1bfa3f41b2a89e5f11fa5d9766 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-f2a05f1bfa3f41b2a89e5f11fa5d97662025-02-03T01:25:26ZengWileyPPAR Research1687-47571687-47652021-01-01202110.1155/2021/66298426629842DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian CancerQianqian Zhao0Jie Zhong1Ping Lu2Xiao Feng3Ying Han4Chenqi Ling5Wenke Guo6Weijin Zhou7Fudong Yu8NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, Shanghai, ChinaDepartment of Gynecology, Shidong Hospital, Yangpu District, Shanghai, ChinaNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shidong Hospital, Yangpu District, Shanghai, ChinaDepartment of Gynecology, Shidong Hospital, Yangpu District, Shanghai, ChinaNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, Shanghai, ChinaNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, Shanghai, ChinaNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, Shanghai, ChinaOvarian carcinoma (OV) is a lethal gynecological malignancy. Most OV patients develop resistance to platinum-based chemotherapy and recurrence. Peroxisome proliferator-activated receptors (PPARs) are the ligand activating transcription factor of the nuclear receptor superfamily. PPARs as important transcriptional regulators regulate important physiological processes such as lipid metabolism, inflammation, and wound healing. Several reports point out that PPARs can also have an effect on the sensitivity of tumor cells to platinum-based chemotherapy drugs. However, the role of PPAR-target related genes (PPAR-TRGs) in chemotherapeutic resistance of OV remains unclear. The present study is aimed at optimizing candidate genes by integrating platinum-chemotherapy expression data and PPAR family genes with their targets. The gene expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. A total of 4 genes (AP2A2, DOCK4, HSDL2, and PDK4) were the candidate differentially expressed genes (DEGs) of PPAR-TRGs with platinum chemosensitivity. After conducting numerous survival analyses using different cohorts, we found that only the upexpression of DOCK4 has important significance with the poor prognosis of OV patients. Meanwhile, DOCK4 is detected in plasma and enriched in neutrophil and monocyte cells of the blood. We further found that there were significant correlations between DOCK4 expression and the levels of CD4+ T cell infiltration, dendritic cell infiltration, and neutrophil infiltration in OV. In addition, we verified the expression level of DOCK4 in OV cell lines treated with platinum drugs and found that DOCK4 is potentially responsive to platinum drugs. In conclusion, DOCK4 is potentially associated with immune cell infiltration and represents a valuable prognostic biomarker in ovarian cancer patients.http://dx.doi.org/10.1155/2021/6629842 |
| spellingShingle | Qianqian Zhao Jie Zhong Ping Lu Xiao Feng Ying Han Chenqi Ling Wenke Guo Weijin Zhou Fudong Yu DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer PPAR Research |
| title | DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer |
| title_full | DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer |
| title_fullStr | DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer |
| title_full_unstemmed | DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer |
| title_short | DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer |
| title_sort | dock4 is a platinum chemosensitive and prognostic related biomarker in ovarian cancer |
| url | http://dx.doi.org/10.1155/2021/6629842 |
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