Transcriptomic Analysis of Organ-Specific Metastasis Regulation in Breast Cancer

¹ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

² Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

³ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

⁴ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

⁵ Baoding NO.1 Hospital, Baoding 071000, Hebei, China,

⁶ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

⁷ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

⁸ Department of Pathology, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China,

PAR 2026 , 10(4), 1–17; https://doi.org/10.26689/par.v10i4.15845

© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Abstract

Objective: This study aimed to investigate the underlying mechanisms of breast cancer metastasis patterns through a transcriptomic analysis of breast cancer with organ-specific metastasis. Methods: (1) Breast cancer cell lines capable of specific lung and bone metastasis were constructed using the PyMT-1 cell line. (2) The IVIS imaging system was employed to screen cell lines with robust specific metastatic capabilities. (3) Transcriptome sequencing was conducted on the resultant breast cancer cell lines exhibiting specific metastasis. (4) The transcriptome sequencing data were analyzed to identify pathways influencing specific metastasis in breast cancer. (5) Validation of pathway-related genes through PCR detection. (6) Clinical validation of differentially expressed genes in paraffin specimens. Results: (1) The IVIS system confirmed the specific metastatic abilities of PyMT-1, Py-L1, Py-L2, Py-B1 and Py-B2 tumors. PyMT-1, Py-L1 and Py-B1 were chosen for further experiments. (2) Following transcriptome sequencing, differentially expressed genes were identified and enrichment analysis was conducted. Pairwise comparisons among the three cell lines revealed 917 differentially expressed genes between PyMT-1 and Py-L1 (including 641 upregulated and 276 downregulated genes); 4131 differentially expressed genes between PyMT-1 and Py-B1 (including 2158 upregulated and 1973 downregulated genes). Conclusions: This study analyzed the genetic background related to breast cancer-specific lung and bone metastasis at the transcriptome level. Obtained the corresponding differential expression profiles and potential functional pathways involved. Demonstrated the promoting roles of CCN2 and ITGB6 in breast cancer lung metastasis, and the promoting roles of CD44 and THBS1 in breast cancer bone metastasis.

References

Xia C, Dong X, Li H, et al., 2022, Cancer Statistics in China and the United States, 2022: Profiles, Trends, and Determinants. Chinese Medical Journal, 135(5): 584–590.

Koboldt DC, Fulton RS, McLellan MD, et al., 2012, Comprehensive Molecular Portraits of Human Breast Tumours. Nature, 490(7418): 61–70.

Allemani C, Matsuda T, Di Carlo V, et al., 2018, Global Surveillance of Trends in Cancer Survival 2000–14 (CONCORD-3): Analysis of Individual Records for 37 513 025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries. The Lancet, 391(10125): 1023–1075.

Zbinden A, Layland SL, Urbanczyk M, et al., 2021, Nidogen-1 Mitigates Ischemia and Promotes Tissue Survival and Regeneration. Advanced Science, 8(4): 2002500.

Wculek SK, Malanchi I., 2015, Neutrophils Support Lung Colonization of Metastasis-Initiating Breast Cancer Cells. Nature, 528(7582): 413–417.

Deepak KGK, Vempati R, Nagaraju GP, et al., 2020, Tumor Microenvironment: Challenges and Opportunities in Targeting Metastasis of Triple Negative Breast Cancer. Pharmacological Research, 153: 104683.

Malanchi I, Santamaria-Martínez A, Susanto E, et al., 2012, Interactions Between Cancer Stem Cells and Their Niche Govern Metastatic Colonization. Nature, 481(7379): 85–89.

Wang Y, Li Y, Zhong J, et al., 2023, Tumor-Derived Cav-1 Promotes Pre-Metastatic Niche Formation and Lung Metastasis in Breast Cancer. Theranostics, 13(5): 1684–1697.

Gao D, Joshi N, Choi H, et al., 2012, Myeloid Progenitor Cells in the Premetastatic Lung Promote Metastases by Inducing Mesenchymal to Epithelial Transition. Cancer Research, 72(6): 1384–1394.

Hongu T, Pein M, Insua-Rodríguez J, et al., 2022, Perivascular Tenascin C Triggers Sequential Activation of Macrophages and Endothelial Cells to Generate a Pro-Metastatic Vascular Niche in the Lungs. Nature Cancer, 3(4): 486–504.

Ghosh P, Dey A, Nandi S, et al., 2025, CTGF (CCN2): A Multifaceted Mediator in Breast Cancer Progression and Therapeutic Targeting. Cancer Metastasis Reviews, 44(1): 32.

Lee SG, Su ZZ, Emdad L, et al., 2008, Astrocyte Elevated Gene-1 Activates Cell Survival Pathways Through PI3K-Akt Signaling. Oncogene, 27(8): 1114–1121.

Gangoda L, Liem M, Ang C, et al., 2017, Proteomic Profiling of Exosomes Secreted by Breast Cancer Cells with Varying Metastatic Potential. PROTEOMICS, 17(23–24): 1600370.

Guise TA., 2013, Breast Cancer Bone Metastases: It's All About the Neighborhood. Cell, 154(5): 957–959.

Ye J, Baer JM, Faget DV, et al., 2024, Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression. Cancer Discovery, 14(7): 1302–1323.

Kiesel L, Kohl A., 2016, Role of the RANK/RANKL Pathway in Breast Cancer. Maturitas, 86: 10–16.

Wan L, Pantel K, Kang Y., 2013, Tumor Metastasis: Moving New Biological Insights into the Clinic. Nature Medicine, 19(11): 1450–1464.

Zhang XHF, Jin X, Malladi S, et al., 2013, Selection of Bone Metastasis Seeds by Mesenchymal Signals in the Primary Tumor Stroma. Cell, 154(5): 1060–1073.

Liang Y, Zhang H, Song X, et al., 2020, Metastatic Heterogeneity of Breast Cancer: Molecular Mechanism and Potential Therapeutic Targets. Seminars in Cancer Biology, 60: 14–27.

Quail DF, Joyce JA, 2013, Microenvironmental Regulation of Tumor Progression and Metastasis. Nature Medicine, 19(11): 1423–1437.

Johnson RW, Finger EC, Olcina MM, et al., 2016, Erratum: Induction of LIFR Confers a Dormancy Phenotype in Breast Cancer Cells Disseminated to the Bone Marrow. Nature Cell Biology, 18(11): 1260–1260.

Balz LM, Bartkowiak K, Andreas A, et al., 2012, The Interplay of HER2/HER3/PI3K and EGFR/HER2/PLC-γ1 Signaling in Breast Cancer Cell Migration and Dissemination. The Journal of Pathology, 227(2): 234–244.

Labrèche C, Cook DP, Abou-Hamad J, et al., 2021, Periostin Gene Expression in Neu-Positive Breast Cancer Cells Is Regulated by a FGFR Signaling Cross Talk with TGFβ/PI3K/AKT Pathways. Breast Cancer Research, 23(1): 107.

Jin L, Han B, Siegel E, et al., 2018, Breast Cancer Lung Metastasis: Molecular Biology and Therapeutic Implications. Cancer Biology & Therapy, 19(10): 858–868.

Morra L, Moch H., 2011, Periostin Expression and Epithelial-Mesenchymal Transition in Cancer: A Review and an Update. Virchows Archiv, 459(5): 465–475.

Lin S, Zhou M, Cheng L, et al., 2024, Exploring the Association of POSTN+ Cancer-Associated Fibroblasts with Triple-Negative Breast Cancer. International Journal of Biological Macromolecules, 268(Pt 1): 131560.

Jia L, Li G, Ma N, et al., 2022, Soluble POSTN Is a Novel Biomarker Complementing CA153 and CEA for Breast Cancer Diagnosis and Metastasis Prediction. BMC Cancer, 22(1): 760.

Previous article in this issue

Next article in this issue