Retrospective study of transcriptomic profiling identifies Thai triple-negative breast cancer patients who may benefit from immune checkpoint and PARP inhibitors

PeerJ

article

Monthira Suntiparpluacha¹  Jantappapa Chanthercrob¹  Doonyapat Sa-nguanraksa²  Juthamas Sitthikornpaiboon¹  Amphun Chaiboonchoe¹  Patipark Kueanjinda³  Natini Jinawath⁴  Somponnat Sampattavanich¹ 

[1] Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University;Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University;Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University;Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University;Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University;Integrative Computational BioScience ,(ICBS) Center, Mahidol University

关键词: Gene expression;    Triple-negative breast cancer;    Subtype;    NanoString nCounter;   

DOI  :  10.7717/peerj.15350

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundTriple-negative breast cancer (TNBC) is a rare and aggressive breast cancer subtype. Unlike the estrogen receptor-positive subtype, whose recurrence risk can be predicted by gene expression-based signature, TNBC is more heterogeneous, with diverse drug sensitivity levels to standard regimens. This study explored the benefit of gene expression-based profiling for classifying the molecular subtypes of Thai TNBC patients.MethodsThe nCounter-based Breast 360 gene expression was used to classify Thai TNBC retrospective cohort subgroups. Their expression profiles were then compared against the previously established TNBC classification system. The differential characteristics of the tumor microenvironment and DNA damage repair signatures across subgroups were also explored.ResultsThai TNBC cohort could be classified into four main subgroups, corresponding to the LAR, BL-2, and M subtypes based on Lehmann’s TNBC classification. The PAM50 gene set classified most samples as basal-like subtypes except for Group 1. Group 1 exhibited similar enrichment of the metabolic and hormone response pathways to the LAR subtype. Group 2 shared pathway activation with the BL-2 subtype. Group 3 showed an increase in the EMT pathway, similar to the M subtype. Group 4 showed no correlation with Lehmann’s TNBC. The tumor microenvironment (TME) analysis showed high TME cell abundance with increased expression of immune blockade genes in Group 2. Group 4 exhibited low TME cell abundance and reduced immune blockade gene expressions. We also observed distinct signatures of the DNA double-strand break repair genes in Group 1.ConclusionsOur study reported unique characteristics between the four TNBC subgroups and showed the potential use of immune checkpoint and PARP inhibitors in subsets of Thai TNBC patients. Our findings warrant further clinical investigation to validate TNBC’s sensitivity to these regimens.

【 授权许可】

CC BY