title: Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.
abstract: In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44+mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
authors.forename: Xian-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine-Neurology, General Hospital of Chinese People's Armed Police Forces, 69 Yongding Road, Beijing, 100039, China.
authors.forename: Jia-Peng
authors.initials: JP
authors.lastname: Zhou
authors.affiliation: Department of Biotherapy Center, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Mu
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Harbin Medical University, 148 Baojian Road, Harbin, 150086, China.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
authors.forename: You-Xue
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China. rxwkpd@126.com.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C497483:CD44 protein, human
keywords: Biomarker; Breast cancer stem cell; HER2-positive; Transcriptome sequencing