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

PeerJ. 2023 Jun 12:11:e15350. doi: 10.7717/peerj.15350. eCollection 2023.

Abstract

Background: Triple-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.

Methods: The 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.

Results: Thai 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.

Conclusions: Our 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.

Keywords: Gene expression; NanoString nCounter; Subtype; Triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • Retrospective Studies
  • Southeast Asian People
  • Transcriptome*
  • Triple Negative Breast Neoplasms* / drug therapy
  • Tumor Microenvironment / genetics

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Immune Checkpoint Inhibitors

Grants and funding

This research project was supported by Mahidol University and The Foundation for Cancer Care Siriraj Hospital. Natini Jinawath is a recipient of mid-career research grant (#N41A640161) from the National Research Council of Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.