Peripheral Blood Transcriptome Identifies High-risk Benign and Malignant Breast Lesions

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Jun 5

PMID 32497068

Citations 11

Authors

Hong Hou

Yali Lyu

Jing Jiang

Min Wang

Ruirui Zhang

Choong-Chin Liew

Binggao Wang

Changming Cheng

Affiliations

Soon will be listed here.

Abstract

Background: Peripheral blood transcriptome profiling is a potentially important tool for disease detection. We utilize this technique in a case-control study to identify candidate transcriptomic biomarkers able to differentiate women with breast lesions from normal controls.

Methods: Whole blood samples were collected from 50 women with high-risk breast lesions, 57 with breast cancers and 44 controls (151 samples). Blood gene expression profiling was carried out using microarray hybridization. We identified blood gene expression signatures using AdaBoost, and constructed a predictive model differentiating breast lesions from controls. Model performance was then characterized by AUC sensitivity, specificity and accuracy. Biomarker biological processes and functions were analyzed for clues to the pathogenesis of breast lesions.

Results: Ten gene biomarkers were identified (YWHAQ, BCLAF1, WSB1, PBX2, DDIT4, LUC7L3, FKBP1A, APP, HERC2P2, FAM126B). A ten-gene panel predictive model showed discriminatory power in the test set (sensitivity: 100%, specificity: 84.2%, accuracy: 93.5%, AUC: 0.99). These biomarkers were involved in apoptosis, TGF-beta signaling, adaptive immune system regulation, gene transcription and post-transcriptional protein modification.

Conclusion: A promising method for the detection of breast lesions is reported. This study also sheds light on breast cancer/immune system interactions, providing clues to new targets for breast cancer immune therapy.

Citing Articles

Expression-Based Diagnosis, Treatment Selection, and Drug Development for Breast Cancer.

Ye Q, Wang J, Ducatman B, Raese R, Rogers J, Wan Y Int J Mol Sci. 2023; 24(13).

PMID: 37445737 PMC: 10342177. DOI: 10.3390/ijms241310561.

Blood-Based mRNA Tests as Emerging Diagnostic Tools for Personalised Medicine in Breast Cancer.

celesnik H, Potocnik U Cancers (Basel). 2023; 15(4).

PMID: 36831426 PMC: 9954278. DOI: 10.3390/cancers15041087.

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival.

Barron-Gallardo C, Garcia-Chagollan M, Moran-Mendoza A, Delgadillo-Cristerna R, Martinez-Silva M, Villasenor-Garcia M Front Genet. 2022; 13:991706.

PMID: 36338974 PMC: 9634254. DOI: 10.3389/fgene.2022.991706.

[miR-16-5p regulates apoptosis and migration of drug-resistant breast cancer cells by targeting YWHAQ].

Zhu H, Mao H, Tao S, Wang W, Chen C, Yang Q Nan Fang Yi Ke Da Xue Xue Bao. 2022; 42(10):1476-1485.

PMID: 36329581 PMC: 9637507. DOI: 10.12122/j.issn.1673-4254.2022.10.06.

Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels.

Lin X, Gu Y, Su Y, Dong Y, Major P, Kapoor A Cancers (Basel). 2022; 14(11).

PMID: 35681785 PMC: 9179637. DOI: 10.3390/cancers14112805.

References

Shou W, Aghdasi B, Armstrong D, Guo Q, Bao S, Charng M . Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12. Nature. 1998; 391(6666):489-92. DOI: 10.1038/35146. View

Liong M, Lim C, Yang H, Chao S, Bong C, Leong W . Blood-based biomarkers of aggressive prostate cancer. PLoS One. 2012; 7(9):e45802. PMC: 3461021. DOI: 10.1371/journal.pone.0045802. View

Hartmann L, Radisky D, Frost M, Santen R, Vierkant R, Benetti L . Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res (Phila). 2014; 7(2):211-7. PMC: 4167687. DOI: 10.1158/1940-6207.CAPR-13-0222. View

Archange C, Nowak J, Garcia S, Moutardier V, Calvo E, Dagorn J . The WSB1 gene is involved in pancreatic cancer progression. PLoS One. 2008; 3(6):e2475. PMC: 2423480. DOI: 10.1371/journal.pone.0002475. View

Vazquez A, Bond E, Levine A, Bond G . The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug Discov. 2008; 7(12):979-87. DOI: 10.1038/nrd2656. View

Cao J, Wang Y, Dong R, Lin G, Zhang N, Wang J . Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells. Cancer Res. 2015; 75(22):4839-51. DOI: 10.1158/0008-5472.CAN-15-0711. View

Sun L, Legood R, Sadique Z, Dos-Santos-Silva I, Yang L . Cost-effectiveness of risk-based breast cancer screening programme, China. Bull World Health Organ. 2018; 96(8):568-577. PMC: 6083393. DOI: 10.2471/BLT.18.207944. View

Han M, Liew C, Zhang H, Chao S, Zheng R, Yip K . Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin Cancer Res. 2008; 14(2):455-60. DOI: 10.1158/1078-0432.CCR-07-1801. View

Dennis M, McGhee N, Jefferson L, Kimball S . Regulated in DNA damage and development 1 (REDD1) promotes cell survival during serum deprivation by sustaining repression of signaling through the mechanistic target of rapamycin in complex 1 (mTORC1). Cell Signal. 2013; 25(12):2709-16. PMC: 3867791. DOI: 10.1016/j.cellsig.2013.08.038. View

10.

Vourtsis A, Berg W . Breast density implications and supplemental screening. Eur Radiol. 2018; 29(4):1762-1777. PMC: 6420861. DOI: 10.1007/s00330-018-5668-8. View

11.

Sung H, Rosenberg P, Chen W, Hartman M, Lim W, Chia K . Female breast cancer incidence among Asian and Western populations: more similar than expected. J Natl Cancer Inst. 2015; 107(7). PMC: 4651040. DOI: 10.1093/jnci/djv107. View

12.

Abay M, Tuke G, Zewdie E, Abraha T, Grum T, Brhane E . Breast self-examination practice and associated factors among women aged 20-70 years attending public health institutions of Adwa town, North Ethiopia. BMC Res Notes. 2018; 11(1):622. PMC: 6114883. DOI: 10.1186/s13104-018-3731-9. View

13.

Dentice M, Bandyopadhyay A, Gereben B, Callebaut I, Christoffolete M, Kim B . The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nat Cell Biol. 2005; 7(7):698-705. PMC: 1761694. DOI: 10.1038/ncb1272. View

14.

Hidalgo M, Rowinsky E . The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 2001; 19(56):6680-6. DOI: 10.1038/sj.onc.1204091. View

15.

Pinto J, Rolfo C, Raez L, Prado A, Araujo J, Bravo L . In silico evaluation of DNA Damage Inducible Transcript 4 gene (DDIT4) as prognostic biomarker in several malignancies. Sci Rep. 2017; 7(1):1526. PMC: 5431475. DOI: 10.1038/s41598-017-01207-3. View

16.

Ogawa M . Differentiation and proliferation of hematopoietic stem cells. Blood. 1993; 81(11):2844-53. View

17.

Salsman J, Stathakis A, Parker E, Chung D, Anthes L, Koskowich K . PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4. Sci Rep. 2017; 7:45038. PMC: 5362932. DOI: 10.1038/srep45038. View

18.

Malmartel A, Tron A, Caulliez S . Accuracy of clinical breast examination's abnormalities for breast cancer screening: cross-sectional study. Eur J Obstet Gynecol Reprod Biol. 2019; 237:1-6. DOI: 10.1016/j.ejogrb.2019.04.003. View

19.

Sung H, Rosenberg P, Chen W, Hartman M, Lim W, Chia K . The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations. Int J Cancer. 2016; 139(3):527-34. PMC: 6755674. DOI: 10.1002/ijc.30095. View

20.

Bleyer A, Welch H . Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012; 367(21):1998-2005. DOI: 10.1056/NEJMoa1206809. View