Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

Xing Ji; Jia Li; Yonghua Huang; Pi-Lin Sung; Yuying Yuan; Qiang Liu; Yan Chen; Jia Ju; Yafeng Zhou; Shujia Huang; Fang Chen; Yuan Han; Wen Yuan; Cheng Fan; Qiang Zhao; Haitao Wu; Suihua Feng; Weiqiang Liu; Zhihua Li; Jingsi Chen; Min Chen; Hong Yao; Li Zeng; Tao Ma; Shushu Fan; Jinman Zhang; Ka Yiu Yuen; So Hin Cheng; Irene Wing Shan Chik; Nien-Tzu Liu; Jianyu Zhu; Siyuan Lin; Jeremy Cao; Steve Tong; Zhiyuan Shan; Wenyan Li; Mohammad Reza Hekmat; Masoud Garshasbi; Javier Suela; Yaima Torres; Juan C. Cigudosa; F. J. Pérez  Ruiz; Laura Rodríguez; Mónica García; Janez Bernik; Eva Traven; Ursula Res; Natasa Tul; Ching-Fong Tseng; Depeng Zhao; Luming Sun; Qiong Pan; Li Shen; Mengyao Dai; Yuying Wang; Jian Wang; Huanming Yang; Ye Yin; Tao Duan; Baosheng Zhu; Mahesh Choolani; Xin Jin; Yingwei Chen; Mao Mao

doi:10.1038/s41436-019-0510-5

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

Xing Ji, Jia Li, Yonghua Huang, Pi-Lin Sung, Yuying Yuan, Qiang Liu, Yan Chen, Jia Ju, Yafeng Zhou, Shujia Huang, Fang Chen, Yuan Han, Wen Yuan, Cheng Fan, Qiang Zhao, Haitao Wu, Suihua Feng, Weiqiang Liu, Zhihua Li, Jingsi ChenMin Chen, Hong Yao, Li Zeng, Tao Ma, Shushu Fan, Jinman Zhang, Ka Yiu Yuen, So Hin Cheng, Irene Wing Shan Chik, Nien-Tzu Liu, Jianyu Zhu, Siyuan Lin, Jeremy Cao, Steve Tong, Zhiyuan Shan, Wenyan Li, Mohammad Reza Hekmat, Masoud Garshasbi, Javier Suela, Yaima Torres, Juan C. Cigudosa, F. J. Pérez Ruiz, Laura Rodríguez, Mónica García, Janez Bernik, Eva Traven, Ursula Res, Natasa Tul, Ching-Fong Tseng, Depeng Zhao, Luming Sun, Qiong Pan, Li Shen, Mengyao Dai, Yuying Wang, Jian Wang, Huanming Yang, Ye Yin, Tao Duan, Baosheng Zhu, Mahesh Choolani, Xin Jin, Yingwei Chen, Mao Mao

Genome Research and Molecular Bio Medicine

7 Citations (Scopus)

Abstract

Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Results: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. Conclusion: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

Original language	English
Journal	Genetics in Medicine
Volume	21
Issue number	10
Pages (from-to)	2293-2302
ISSN	1098-3600
DOIs	https://doi.org/10.1038/s41436-019-0510-5
Publication status	Published - 1 Oct 2019

Keywords

Noninvasive prenatal screening test
Maternal malignancy
Multiple chromosomal aneuploidies
Cancer detection
Plasma tumor marker

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41436-019-0510-5

http://www.gimjournal.org/article/S1098360021045093/pdf

Cite this

Ji, X., Li, J., Huang, Y., Sung, P-L., Yuan, Y., Liu, Q., Chen, Y., Ju, J., Zhou, Y., Huang, S., Chen, F., Han, Y., Yuan, W., Fan, C., Zhao, Q., Wu, H., Feng, S., Liu, W., Li, Z., ... Mao, M. (2019). Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests. Genetics in Medicine, 21(10), 2293-2302. https://doi.org/10.1038/s41436-019-0510-5

Ji, X, Li, J, Huang, Y, Sung, P-L, Yuan, Y, Liu, Q, Chen, Y, Ju, J, Zhou, Y, Huang, S, Chen, F, Han, Y, Yuan, W, Fan, C, Zhao, Q, Wu, H, Feng, S, Liu, W, Li, Z, Chen, J, Chen, M, Yao, H, Zeng, L, Ma, T, Fan, S, Zhang, J, Yuen, KY, Cheng, SH, Chik, IWS, Liu, N-T, Zhu, J, Lin, S, Cao, J, Tong, S, Shan, Z, Li, W, Hekmat, MR, Garshasbi, M, Suela, J, Torres, Y, Cigudosa, JC, Ruiz, FJP, Rodríguez, L, García, M, Bernik, J, Traven, E, Res, U, Tul, N, Tseng, C-F, Zhao, D, Sun, L, Pan, Q, Shen, L, Dai, M, Wang, Y, Wang, J, Yang, H, Yin, Y, Duan, T, Zhu, B, Choolani, M, Jin, X, Chen, Y & Mao, M 2019, 'Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests', Genetics in Medicine, vol. 21, no. 10, pp. 2293-2302. https://doi.org/10.1038/s41436-019-0510-5

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title = "Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests",

abstract = "Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Results: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. Conclusion: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.",

keywords = "Noninvasive prenatal screening test, Maternal malignancy, Multiple chromosomal aneuploidies, Cancer detection, Plasma tumor marker",

author = "Xing Ji and Jia Li and Yonghua Huang and Pi-Lin Sung and Yuying Yuan and Qiang Liu and Yan Chen and Jia Ju and Yafeng Zhou and Shujia Huang and Fang Chen and Yuan Han and Wen Yuan and Cheng Fan and Qiang Zhao and Haitao Wu and Suihua Feng and Weiqiang Liu and Zhihua Li and Jingsi Chen and Min Chen and Hong Yao and Li Zeng and Tao Ma and Shushu Fan and Jinman Zhang and Yuen, {Ka Yiu} and Cheng, {So Hin} and Chik, {Irene Wing Shan} and Nien-Tzu Liu and Jianyu Zhu and Siyuan Lin and Jeremy Cao and Steve Tong and Zhiyuan Shan and Wenyan Li and Hekmat, {Mohammad Reza} and Masoud Garshasbi and Javier Suela and Yaima Torres and Cigudosa, {Juan C.} and Ruiz, {F. J. P{\'e}rez} and Laura Rodr{\'i}guez and M{\'o}nica Garc{\'i}a and Janez Bernik and Eva Traven and Ursula Res and Natasa Tul and Ching-Fong Tseng and Depeng Zhao and Luming Sun and Qiong Pan and Li Shen and Mengyao Dai and Yuying Wang and Jian Wang and Huanming Yang and Ye Yin and Tao Duan and Baosheng Zhu and Mahesh Choolani and Xin Jin and Yingwei Chen and Mao Mao",

year = "2019",

month = oct,

day = "1",

doi = "10.1038/s41436-019-0510-5",

language = "English",

volume = "21",

pages = "2293--2302",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "nature publishing group",

number = "10",

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TY - JOUR

T1 - Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

AU - Ji, Xing

AU - Li, Jia

AU - Huang, Yonghua

AU - Sung, Pi-Lin

AU - Yuan, Yuying

AU - Liu, Qiang

AU - Chen, Yan

AU - Ju, Jia

AU - Zhou, Yafeng

AU - Huang, Shujia

AU - Chen, Fang

AU - Han, Yuan

AU - Yuan, Wen

AU - Fan, Cheng

AU - Zhao, Qiang

AU - Wu, Haitao

AU - Feng, Suihua

AU - Liu, Weiqiang

AU - Li, Zhihua

AU - Chen, Jingsi

AU - Chen, Min

AU - Yao, Hong

AU - Zeng, Li

AU - Ma, Tao

AU - Fan, Shushu

AU - Zhang, Jinman

AU - Yuen, Ka Yiu

AU - Cheng, So Hin

AU - Chik, Irene Wing Shan

AU - Liu, Nien-Tzu

AU - Zhu, Jianyu

AU - Lin, Siyuan

AU - Cao, Jeremy

AU - Tong, Steve

AU - Shan, Zhiyuan

AU - Li, Wenyan

AU - Hekmat, Mohammad Reza

AU - Garshasbi, Masoud

AU - Suela, Javier

AU - Torres, Yaima

AU - Cigudosa, Juan C.

AU - Ruiz, F. J. Pérez

AU - Rodríguez, Laura

AU - García, Mónica

AU - Bernik, Janez

AU - Traven, Eva

AU - Res, Ursula

AU - Tul, Natasa

AU - Tseng, Ching-Fong

AU - Zhao, Depeng

AU - Sun, Luming

AU - Pan, Qiong

AU - Shen, Li

AU - Dai, Mengyao

AU - Wang, Yuying

AU - Wang, Jian

AU - Yang, Huanming

AU - Yin, Ye

AU - Duan, Tao

AU - Zhu, Baosheng

AU - Choolani, Mahesh

AU - Jin, Xin

AU - Chen, Yingwei

AU - Mao, Mao

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Results: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. Conclusion: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

AB - Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Results: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. Conclusion: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

KW - Noninvasive prenatal screening test

KW - Maternal malignancy

KW - Multiple chromosomal aneuploidies

KW - Cancer detection

KW - Plasma tumor marker

U2 - 10.1038/s41436-019-0510-5

DO - 10.1038/s41436-019-0510-5

M3 - Journal article

C2 - 30976098

SN - 1098-3600

VL - 21

SP - 2293

EP - 2302

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 10

ER -

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

Abstract

Keywords

UN SDGs

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