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Peer-reviewedCC BY-NC-ND 4.0Cancer Genomics & Proteomics

High LAT1 Expression Is Associated With CD163⁺ Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

  • YUN-SHAN LIN1
  • SHU-FEN CHIANG2
  • TSUNG-WEI CHEN3
  • JHEN-YU CHEN4
  • TAO-WEI KE5,6
  • YUAN-YAO TSAI5
  • K S CLIFFORD CHAO4,7,8
  • KEVIN CHIH-YANG HUANG9,10,11,12
12 affiliations
  1. 1Department of Pathology, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  2. 2Lab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan, R.O.C.
  3. 3Department of Pathology, Asia University Hospital, Asia University, Taichung, Taiwan, R.O.C.
  4. 4Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  5. 5Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  6. 6School of Chinese Medicine & Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
  7. 7Department of Radiation Oncology, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  8. 8Department of Radiotherapy, School of Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  9. 9Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, R.O.C.
  10. 10Translation Research Core, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
  11. 11Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan, R.O.C.
  12. 12Office of Research and Development, Asia University, Taichung, Taiwan, R.O.C.
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Abstract

Background/Aim: Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks targeted therapy, and robust prognostic biomarkers remain scarce. L-type amino acid transporter 1 (LAT1/SLC7A5) drives tumor amino acid metabolism and proliferation, whereas CD163+ M2-like tumor-associated macrophages (TAMs) constitute a hallmark of an immunosuppressive microenvironment.

Patients and Methods: We investigated the expression, clinicopathological associations, and prognostic significance of tumor LAT1 and CD163+ macrophage density in 172 patients with TNBC. LAT1 and CD163 were assessed by immunohistochemistry and dichotomized at the cohort median.

Results: High LAT1 expression was strongly associated with high histologic grade, larger tumor size, advanced stage, and elevated Ki-67 (all p<0.001) and predicted inferior overall survival (OS) and disease-free survival (DFS; both p<0.05). CD163+ macrophage density showed no association with conventional clinicopathological features. LAT1 and CD163 expression were weakly but significantly correlated (Pearson’s r=0.191, p=0.012; Spearman’s ρ=0.220, p=0.004). In multivariable analysis, the adjusted DFS associations of both markers were model-dependent: high CD163 was independently associated with DFS after adjustment for tumor size [hazard ratio (HR)=2.11, p=0.034] but only borderline after ordinal-stage adjustment (HR=1.87, p=0.076), and the LAT1 effect on DFS was likewise stage-dependent. For OS, high LAT1 remained independently prognostic after adjustment for stage and age (HR=3.6, p=0.02), whereas CD163 did not.

Conclusion: These findings indicate that LAT1 and CD163 convey significant prognostic information in TNBC and support the further evaluation of LAT1-directed metabolic and macrophage-targeted therapeutic strategies.

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Cite

BibTeXRIS
BibTeX
@article{yunshan2026high,
  title = {{High LAT1 Expression Is Associated With CD163⁺ Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer}},
  author = {YUN-SHAN LIN and SHU-FEN CHIANG and TSUNG-WEI CHEN and JHEN-YU CHEN and TAO-WEI KE and YUAN-YAO TSAI and K S CLIFFORD CHAO and KEVIN CHIH-YANG HUANG},
  journal = {Cancer Genomics \& Proteomics},
  year = {2026},
  month = oct,
  doi = {10.21873/cgp.20625},
  url = {https://doi.org/10.21873/cgp.20625},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - High LAT1 Expression Is Associated With CD163⁺ Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer
AU  - YUN-SHAN LIN
AU  - SHU-FEN CHIANG
AU  - TSUNG-WEI CHEN
AU  - JHEN-YU CHEN
AU  - TAO-WEI KE
AU  - YUAN-YAO TSAI
AU  - K S CLIFFORD CHAO
AU  - KEVIN CHIH-YANG HUANG
PY  - 2026
DA  - 2026/10/31
JO  - Cancer Genomics & Proteomics
DO  - 10.21873/cgp.20625
UR  - https://doi.org/10.21873/cgp.20625
AB  - Background/Aim: Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks targeted therapy, and robust prognostic biomarkers remain scarce. L-type amino acid transporter 1 (LAT1/SLC7A5) drives tumor amino acid metabolism and proliferation, whereas CD163+ M2-like tumor-associated macrophages (TAMs) constitute a hallmark of an immunosuppressive microenvironment.  Patients and Methods: We investigated the expression, clinicopathological associations, and prognostic significance of tumor LAT1 and CD163+ macrophage density in 172 patients with TNBC. LAT1 and CD163 were assessed by immunohistochemistry and dichotomized at the cohort median.  Results: High LAT1 expression was strongly associated with high histologic grade, larger tumor size, advanced stage, and elevated Ki-67 (all p<0.001) and predicted inferior overall survival (OS) and disease-free survival (DFS; both p<0.05). CD163+ macrophage density showed no association with conventional clinicopathological features. LAT1 and CD163 expression were weakly but significantly correlated (Pearson’s r=0.191, p=0.012; Spearman’s ρ=0.220, p=0.004). In multivariable analysis, the adjusted DFS associations of both markers were model-dependent: high CD163 was independently associated with DFS after adjustment for tumor size [hazard ratio (HR)=2.11, p=0.034] but only borderline after ordinal-stage adjustment (HR=1.87, p=0.076), and the LAT1 effect on DFS was likewise stage-dependent. For OS, high LAT1 remained independently prognostic after adjustment for stage and age (HR=3.6, p=0.02), whereas CD163 did not.  Conclusion: These findings indicate that LAT1 and CD163 convey significant prognostic information in TNBC and support the further evaluation of LAT1-directed metabolic and macrophage-targeted therapeutic strategies.
SN  - 1109-6535
SN  - 1790-6245
ER  -