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. 2025 Aug 31:44:102210.
doi: 10.1016/j.bbrep.2025.102210. eCollection 2025 Dec.

Collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes by functional proteomics from core needle biopsy samples of Taiwanese breast cancer

Wei-Chi Ku  1 , Nam Nhut Phan  2 , Chih-Yi Liu  1   3 , Chi-Jung Huang  4   5 , Chen-Chung Liao  6 , Yen-Chun Huang  7 , Po-Hsin Kong  7 , Ling-Ming Tseng  8   9 , Chi-Cheng Huang  8   9   10
Affiliations

Collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes by functional proteomics from core needle biopsy samples of Taiwanese breast cancer

Wei-Chi Ku et al. Biochem Biophys Rep. .

Abstract

Purpose: This study aimed to conduct functional proteomics across breast cancer subtypes with bioinformatics analyses.

Methods: Candidate proteins were identified using nanoscale liquid chromatography with tandem mass spectrometry (NanoLC-MS/MS) from core needle biopsy samples of early stage (0-III) breast cancers, followed by external validation with public domain gene-expression datasets (TCGA TARGET GTEx and TCGA BRCA).

Results: Seventeen proteins demonstrated significantly differential expression and protein-protein interaction (PPI) found the strong networks including COL2A1, COL11A1, COL6A1, COL6A2, THBS1 and LUM. Public domain databases also showed that COL2A1, COL11A1, COL6A1, COL6A2 and LUM were higher in primary/metastatic tumor than in normal tissue (one-way ANOVA, all P-values less than 0.001), and all six genes were differentially expressed across four molecular subtypes based on hormone receptor (HR) status and human epidermal growth factor receptor II (HER2) status (one-way ANOVA, all P-values less than 0.001). Disease-specific survival discrepancy was observed comparing breast cancer patients of the upper and lower quartile of the collagen family (COL2A1, COL11A1, COL6A1, COL6A2), THBS1 and LUM gene expression signature (log-rank test, P = 0.06).

Conclusion: Functional proteomics suggested that collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes.

Keywords: Breast neoplasms; Collagen; Lumican; Proteomics; Thrombospondin 1.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic design of the study using protein-protein interaction (PPI) with functional proteomics from breast cancer core biopsy samples network. (LC MS/MS: liquid chromatography with tandem mass spectrometry, DE: differentially expressed, ANOVA: analysis of variance).
Fig. 2
Fig. 2
Data process flow for proteomics analysis.
Fig. 3
Fig. 3
Comparison of normalization methods for TMT-based proteomics across 12 batches. Boxplots show protein intensity distributions for each TMT batch (B1–B12) across all samples: (A) Raw (unnormalized) data, (B) Median–median normalization, (C) Row-wise normalization, (D) Internal reference scaling (IRS), and (E) Median polish.
Fig. 4
Fig. 4
Protein-protein interaction network from 17 protein targets (CAST, BCL2L13, COL6A2, PZP, LUM, COL2A1, COL6A1, COL11A1, THBS1, PLIN3, MB, TJP1, SETD7, RPL21, CLIP1, TUBB3 and TNC).
Fig. 5
Fig. 5
mRNA expression profiles from the TCGA TARGET GTEx (n = 1278) database. The expression of COL2A1, COL11A1, COL6A1, COL6A2 and LUM tends to be higher in primary/metastatic tumor than in normal tissue.
Fig. 6
Fig. 6
mRNA expression profiles from the TCGA BRCA (n = 821) database. COL2A1, COL11A1, COL6A1, COL6A2, THBS1 and LUM were differentially expressed across four PAM50 molecular subtypes.
Fig. 7
Fig. 7
Disease-specific free survival from the TCGA BRCA cohort (n = 821). Prognostic discrepancy was observed comparing breast cancer patients of the upper and lower quartile of the collagen family, THBS1 and LUM signature.
See this image and copyright information in PMC

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