Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients
Abstract Background Ovarian cancer (OC) is the deadliest gynecological cancer. The absence of biomarkers in early detection and chemotherapy resistance is a principal cause of treatment failure in OC. Methods In this study, next generation sequencing (NGS) was used to sequence the mRNA of 44 OC pati...
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Wiley
2020-07-01
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Series: | Cancer Medicine |
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Online Access: | https://doi.org/10.1002/cam4.3122 |
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author | Hui Zheng Meiqin Zhang Shuang Ma Wenting Yang Suhong Xie Yanchun Wang Yixuan Liu Jinyan Kai Qian Ma Renquan Lu Lin Guo |
author_facet | Hui Zheng Meiqin Zhang Shuang Ma Wenting Yang Suhong Xie Yanchun Wang Yixuan Liu Jinyan Kai Qian Ma Renquan Lu Lin Guo |
author_sort | Hui Zheng |
collection | DOAJ |
description | Abstract Background Ovarian cancer (OC) is the deadliest gynecological cancer. The absence of biomarkers in early detection and chemotherapy resistance is a principal cause of treatment failure in OC. Methods In this study, next generation sequencing (NGS) was used to sequence the mRNA of 44 OC patients including 14 chemotherapy insensitive and 18 sensitive patients. Differentially expressed genes (DEGs) from OC patients (compared with healthy controls) and chemotherapy sensitive patients (compared with chemotherapy insensitive patients) were identified by edgeR v3.12.0 in R v3.2.2, which were enriched using Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). The common DEGs in cancer occurring and chemotherapy sensitivity were further screened. Among them, genes participating in chemotherapy sensitivity associated pathways were regarded as chemotherapy sensitivity‐related key genes. Quantitative real‐time PCR (qPCR) and immunohistochemistry (IHC) were used to verify the expression of the key genes. Results We found 1588 DEGs between OC patients and healthy controls (HCs), which were mainly enriched in cell cycle pathway. Meanwhile, 249 DEGs were identified between chemotherapy sensitive and insensitive OC patients, which were mainly enriched in MAPK signaling pathway, ERBB signaling pathway, TNF signaling pathway, and IL‐17 signaling pathway. Thirty‐five DEGs were shared in chemotherapy sensitivity group and cancer occurring group. Among them, there are five genes (JUND, JUNB, MUC5B, NRG1, and NR4A1) participating in the above four chemotherapy sensitivity‐related pathways. It is remarkable that JUND is in the upstream of MUC5B in IL‐17 signaling pathway and their expressions were verified by qPCR and IHC. Conclusions The expression levels of the key genes related to chemotherapy sensitivity might be used as biomarkers to predict the treatment outcome and as a target to improve prognosis. |
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institution | Directory Open Access Journal |
issn | 2045-7634 |
language | English |
last_indexed | 2024-12-21T01:23:15Z |
publishDate | 2020-07-01 |
publisher | Wiley |
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series | Cancer Medicine |
spelling | doaj.art-9010984e73eb454baf381234f8a1d5d02022-12-21T19:20:35ZengWileyCancer Medicine2045-76342020-07-019145200520910.1002/cam4.3122Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patientsHui Zheng0Meiqin Zhang1Shuang Ma2Wenting Yang3Suhong Xie4Yanchun Wang5Yixuan Liu6Jinyan Kai7Qian Ma8Renquan Lu9Lin Guo10Department of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Oncology Shanghai Medical College Fudan University Shanghai ChinaGenenexus Technology Corporation Shanghai ChinaGenenexus Technology Corporation Shanghai ChinaDepartment of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Oncology Shanghai Medical College Fudan University Shanghai ChinaDepartment of Oncology Shanghai Medical College Fudan University Shanghai ChinaDepartment of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Clinical Laboratory Fudan University Shanghai Cancer Center Shanghai ChinaAbstract Background Ovarian cancer (OC) is the deadliest gynecological cancer. The absence of biomarkers in early detection and chemotherapy resistance is a principal cause of treatment failure in OC. Methods In this study, next generation sequencing (NGS) was used to sequence the mRNA of 44 OC patients including 14 chemotherapy insensitive and 18 sensitive patients. Differentially expressed genes (DEGs) from OC patients (compared with healthy controls) and chemotherapy sensitive patients (compared with chemotherapy insensitive patients) were identified by edgeR v3.12.0 in R v3.2.2, which were enriched using Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). The common DEGs in cancer occurring and chemotherapy sensitivity were further screened. Among them, genes participating in chemotherapy sensitivity associated pathways were regarded as chemotherapy sensitivity‐related key genes. Quantitative real‐time PCR (qPCR) and immunohistochemistry (IHC) were used to verify the expression of the key genes. Results We found 1588 DEGs between OC patients and healthy controls (HCs), which were mainly enriched in cell cycle pathway. Meanwhile, 249 DEGs were identified between chemotherapy sensitive and insensitive OC patients, which were mainly enriched in MAPK signaling pathway, ERBB signaling pathway, TNF signaling pathway, and IL‐17 signaling pathway. Thirty‐five DEGs were shared in chemotherapy sensitivity group and cancer occurring group. Among them, there are five genes (JUND, JUNB, MUC5B, NRG1, and NR4A1) participating in the above four chemotherapy sensitivity‐related pathways. It is remarkable that JUND is in the upstream of MUC5B in IL‐17 signaling pathway and their expressions were verified by qPCR and IHC. Conclusions The expression levels of the key genes related to chemotherapy sensitivity might be used as biomarkers to predict the treatment outcome and as a target to improve prognosis.https://doi.org/10.1002/cam4.3122chemotherapy sensitivitykey genesNGSovarian cancerpathways |
spellingShingle | Hui Zheng Meiqin Zhang Shuang Ma Wenting Yang Suhong Xie Yanchun Wang Yixuan Liu Jinyan Kai Qian Ma Renquan Lu Lin Guo Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients Cancer Medicine chemotherapy sensitivity key genes NGS ovarian cancer pathways |
title | Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
title_full | Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
title_fullStr | Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
title_full_unstemmed | Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
title_short | Identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
title_sort | identification of the key genes associated with chemotherapy sensitivity in ovarian cancer patients |
topic | chemotherapy sensitivity key genes NGS ovarian cancer pathways |
url | https://doi.org/10.1002/cam4.3122 |
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