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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Breast Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1638758

Spatial gene expression profiling identifies prognostic features of residual tumors after neoadjuvant chemotherapy in triple-negative breast cancer

Provisionally accepted
Hye Sung  WonHye Sung Won1Yong-Seok  KimYong-Seok Kim2Kyung Jin  SeoKyung Jin Seo3Sun-Young  JunSun-Young Jun3Der Sheng  SunDer Sheng Sun1Mihong  ChoiMihong Choi1Jung-Sook  YoonJung-Sook Yoon4Jae Ho  ByunJae Ho Byun1*
  • 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  • 2Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  • 3Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  • 4Clinical Research Laboratory, Uijeongbu St. Mary's Hospital. College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

Background: The standard treatment for early-stage triple-negative breast cancer (TNBC) is neoadjuvant chemotherapy (NAC) followed by surgery, but patients with residual disease have worse outcomes. We investigated genetic alterations related to recurrence using spatial transcriptomic analyses of residual tumors from patients who had and had not relapsed after NAC for early-stage TNBC. Methods: Thirteen patients who underwent curative resection after NAC for early-stage TNBC, six of whom experienced recurrence, were included. The residual tumor tissues were stained and analyzed using the NanoString GeoMx Digital Spatial Profiling platform. Changes in gene expression were presented as fold changes compared with the control group, and genes were considered to be differentially expressed if they had an absolute value of log2-fold change ≥ 2.0 at a false discovery rate of < 0.05. Results: On comparing gene expression in residual cancer cells, eight genes (S100A9, S100A7, CHI3L1, SLPI, SERPINA3, CASP14, URI1, and AZGP1) were found to be significantly upregulated, and 17 (ACTA2, IGFBP4, BGN, TPM2, MYLK, MMP7, HLA-DPB1, CRISPLD1, COL1A2, OLFM4, KRT14, HLA-DPA1, COL1A1, COL3A1, IFI6, IFI27, and A2M) were significantly downregulated in patients with recurrence. On comparing gene expression in macrophages, six genes (SLPI, PABPC1, AZGP1, SUPT7L, RPL22, and FDCSP) were found to be significantly upregulated, and IFI27 was significantly downregulated in patients with recurrence. No genetic alterations with significant differences were found in T cells. No significant change was observed in the density of macrophages between patients with and without recurrence. However, the density of T cells was relatively lower in patients with than in those without recurrence. Conclusion: We identified some differentially expressed genes relevant to oncogenic signaling and immunosuppressive tumor-associated macrophages. These findings provide novel insights into factors affecting prognosis in patients with residual disease after NAC for early-stage TNBC.

Keywords: breast cancer, Neoadjuvant chemotherapy, Spatial transcriptomics, tumorassociated macrophages, Recurrence

Received: 31 May 2025; Accepted: 31 Jul 2025.

Copyright: © 2025 Won, Kim, Seo, Jun, Sun, Choi, Yoon and Byun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jae Ho Byun, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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