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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Main Authors: Hui Zheng, Meiqin Zhang, Shuang Ma, Wenting Yang, Suhong Xie, Yanchun Wang, Yixuan Liu, Jinyan Kai, Qian Ma, Renquan Lu, Lin Guo
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Cancer Medicine
Subjects:
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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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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