Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer
Abstract Background A major impediment in the treatment of ovarian cancer is the relapse of chemotherapy-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying chemotherapy resistance will improve treatment efficacy through gen...
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doaj-022bd7e8d3d04851a6464ab8b2ae46d62020-11-25T02:20:54ZengBMCBMC Cancer1471-24072020-05-0120111110.1186/s12885-020-06922-1Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancerJihoon Choi0Danai G. Topouza1Anastasiya Tarnouskaya2Sean Nesdoly3Madhuri Koti4Qing Ling Duan5Department of Biomedical and Molecular Sciences, Queen’s UniversityDepartment of Biomedical and Molecular Sciences, Queen’s UniversitySchool of Computing, Queen’s UniversitySchool of Computing, Queen’s UniversityDepartment of Biomedical and Molecular Sciences, Queen’s UniversityDepartment of Biomedical and Molecular Sciences, Queen’s UniversityAbstract Background A major impediment in the treatment of ovarian cancer is the relapse of chemotherapy-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying chemotherapy resistance will improve treatment efficacy through genetic testing and novel therapies. Methods Using data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-taxane combination chemotherapy as “chemo-sensitive” (N = 160) and those who had recurrence within 6 months as “chemo-resistant” (N = 110). Univariate and multivariate analysis of expression microarray data were used to identify differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL). Results Differential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were significantly associated with chemotherapy response in HGSOC. VCP and the most significant co-expression network module contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. Both univariate and multivariate analysis findings were successfully replicated in an independent ovarian cancer cohort. Furthermore, we identified 192 cis-eQTLs associated with the expression of network genes and 4 cis-eQTLs associated with BRCA2 expression. Conclusion This study implicates both known and novel genes as well as biological processes underlying response to platinum-taxane-based chemotherapy among HGSOC patients.http://link.springer.com/article/10.1186/s12885-020-06922-1Chemotherapy resistanceCo-expression network analysisValosin containing proteinExpression quantitative trait lociThe Cancer Genome AtlasHigh-grade serous ovarian carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jihoon Choi Danai G. Topouza Anastasiya Tarnouskaya Sean Nesdoly Madhuri Koti Qing Ling Duan |
spellingShingle |
Jihoon Choi Danai G. Topouza Anastasiya Tarnouskaya Sean Nesdoly Madhuri Koti Qing Ling Duan Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer BMC Cancer Chemotherapy resistance Co-expression network analysis Valosin containing protein Expression quantitative trait loci The Cancer Genome Atlas High-grade serous ovarian carcinoma |
author_facet |
Jihoon Choi Danai G. Topouza Anastasiya Tarnouskaya Sean Nesdoly Madhuri Koti Qing Ling Duan |
author_sort |
Jihoon Choi |
title |
Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
title_short |
Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
title_full |
Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
title_fullStr |
Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
title_full_unstemmed |
Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
title_sort |
gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-05-01 |
description |
Abstract Background A major impediment in the treatment of ovarian cancer is the relapse of chemotherapy-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying chemotherapy resistance will improve treatment efficacy through genetic testing and novel therapies. Methods Using data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-taxane combination chemotherapy as “chemo-sensitive” (N = 160) and those who had recurrence within 6 months as “chemo-resistant” (N = 110). Univariate and multivariate analysis of expression microarray data were used to identify differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL). Results Differential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were significantly associated with chemotherapy response in HGSOC. VCP and the most significant co-expression network module contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. Both univariate and multivariate analysis findings were successfully replicated in an independent ovarian cancer cohort. Furthermore, we identified 192 cis-eQTLs associated with the expression of network genes and 4 cis-eQTLs associated with BRCA2 expression. Conclusion This study implicates both known and novel genes as well as biological processes underlying response to platinum-taxane-based chemotherapy among HGSOC patients. |
topic |
Chemotherapy resistance Co-expression network analysis Valosin containing protein Expression quantitative trait loci The Cancer Genome Atlas High-grade serous ovarian carcinoma |
url |
http://link.springer.com/article/10.1186/s12885-020-06922-1 |
work_keys_str_mv |
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