Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer
Platinum-based chemotherapy is still the standard of care after cytoreductive surgery in the first-line treatment for epithelial ovarian cancer. This study aims to integrate novel biomarkers for predicting platinum sensitivity in EOC after initial cytoreductive surgery precisely. To this end, 60 pat...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-09-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.725264/full |
id |
doaj-4b9ed743a4cf4bb19151642c3cff979f |
---|---|
record_format |
Article |
spelling |
doaj-4b9ed743a4cf4bb19151642c3cff979f2021-09-16T04:59:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.725264725264Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian CancerHong Zheng0Tong Shu1Shan Zhu2Chao Zhang3Min Gao4Nan Zhang5Hongguo Wang6Jie Yuan7Zaixian Tai8Xuefeng Xia9Yuting Yi10Yuting Yi11Jin Li12Yanfang Guan13Yanfang Guan14Yang Xiang15Yunong Gao16Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaGeneplus-Shenzhen, Shenzhen, ChinaDepartment of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaGeneplus-Shenzhen, Shenzhen, ChinaGeneplus-Shenzhen, Shenzhen, ChinaGeneplus-Beijing, Beijing, ChinaGeneplus-Beijing, Beijing, ChinaDepartment of Computer Science and Technology, School of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, ChinaGeneplus-Beijing, Beijing, ChinaGeneplus-Beijing, Beijing, ChinaDepartment of Computer Science and Technology, School of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, ChinaPlatinum-based chemotherapy is still the standard of care after cytoreductive surgery in the first-line treatment for epithelial ovarian cancer. This study aims to integrate novel biomarkers for predicting platinum sensitivity in EOC after initial cytoreductive surgery precisely. To this end, 60 patients were recruited from September 2014 to October 2019. Based on the duration of progress-free survival, 44 and 16 patients were assigned to platinum-sensitive and platinum-resistant group, respectively. Next generation sequencing was performed to dissect the genomic features of ovarian tumors obtained from surgery. Multiple genomic variations were compared between two groups, including single-nucleotide variant, single base or indel signature, loss of heterozygosity (LOH), whole-genome duplication (WGD), and others. The results demonstrated that patients with characteristics including positive SBS10a signature (p < 0.05), or FAM175A LOH (p < 0.01), or negative WGD (p < 0.01) were significantly enriched in platinum-sensitive group. Consistently, patients with positive SBS10a signature (15.8 vs. 10.1 months, p < 0.05), or FAM175A LOH (16.5 vs. 9.2 months, p < 0.05), or negative WGD (16.5 vs. 9.1 months, p < 0.05) have significantly longer PFS than those without these genetic features. By integrating these three biomarkers, a lasso regression model was employed to train and test for all patients, with the AUC value 0.864 in platinum sensitivity prediction. Notably, 388 ovarian cancer patients from TCGA dataset were leveraged as independent validation cohort with AUC value 0.808, suggesting the favorable performance and reliability of this model.https://www.frontiersin.org/articles/10.3389/fonc.2021.725264/fullbiomarkernext generation sequencingovarian cancerplatinum sensitivityROC curve |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hong Zheng Tong Shu Shan Zhu Chao Zhang Min Gao Nan Zhang Hongguo Wang Jie Yuan Zaixian Tai Xuefeng Xia Yuting Yi Yuting Yi Jin Li Yanfang Guan Yanfang Guan Yang Xiang Yunong Gao |
spellingShingle |
Hong Zheng Tong Shu Shan Zhu Chao Zhang Min Gao Nan Zhang Hongguo Wang Jie Yuan Zaixian Tai Xuefeng Xia Yuting Yi Yuting Yi Jin Li Yanfang Guan Yanfang Guan Yang Xiang Yunong Gao Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer Frontiers in Oncology biomarker next generation sequencing ovarian cancer platinum sensitivity ROC curve |
author_facet |
Hong Zheng Tong Shu Shan Zhu Chao Zhang Min Gao Nan Zhang Hongguo Wang Jie Yuan Zaixian Tai Xuefeng Xia Yuting Yi Yuting Yi Jin Li Yanfang Guan Yanfang Guan Yang Xiang Yunong Gao |
author_sort |
Hong Zheng |
title |
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer |
title_short |
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer |
title_full |
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer |
title_fullStr |
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer |
title_full_unstemmed |
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer |
title_sort |
construction and validation of a platinum sensitivity predictive model with multiple genomic variations for epithelial ovarian cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-09-01 |
description |
Platinum-based chemotherapy is still the standard of care after cytoreductive surgery in the first-line treatment for epithelial ovarian cancer. This study aims to integrate novel biomarkers for predicting platinum sensitivity in EOC after initial cytoreductive surgery precisely. To this end, 60 patients were recruited from September 2014 to October 2019. Based on the duration of progress-free survival, 44 and 16 patients were assigned to platinum-sensitive and platinum-resistant group, respectively. Next generation sequencing was performed to dissect the genomic features of ovarian tumors obtained from surgery. Multiple genomic variations were compared between two groups, including single-nucleotide variant, single base or indel signature, loss of heterozygosity (LOH), whole-genome duplication (WGD), and others. The results demonstrated that patients with characteristics including positive SBS10a signature (p < 0.05), or FAM175A LOH (p < 0.01), or negative WGD (p < 0.01) were significantly enriched in platinum-sensitive group. Consistently, patients with positive SBS10a signature (15.8 vs. 10.1 months, p < 0.05), or FAM175A LOH (16.5 vs. 9.2 months, p < 0.05), or negative WGD (16.5 vs. 9.1 months, p < 0.05) have significantly longer PFS than those without these genetic features. By integrating these three biomarkers, a lasso regression model was employed to train and test for all patients, with the AUC value 0.864 in platinum sensitivity prediction. Notably, 388 ovarian cancer patients from TCGA dataset were leveraged as independent validation cohort with AUC value 0.808, suggesting the favorable performance and reliability of this model. |
topic |
biomarker next generation sequencing ovarian cancer platinum sensitivity ROC curve |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.725264/full |
work_keys_str_mv |
AT hongzheng constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT tongshu constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT shanzhu constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT chaozhang constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT mingao constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT nanzhang constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT hongguowang constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT jieyuan constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT zaixiantai constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT xuefengxia constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yutingyi constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yutingyi constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT jinli constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yanfangguan constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yanfangguan constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yangxiang constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer AT yunonggao constructionandvalidationofaplatinumsensitivitypredictivemodelwithmultiplegenomicvariationsforepithelialovariancancer |
_version_ |
1717378389091811328 |