Proteomic alterations in early-stage breast cancer: insights from tumor-adjacent normal tissues analysis

Background

Molecular characterization, such as genomic and transcriptomic profiling, has been incorporated into clinical practice for classifying and selecting treatments for breast cancer patients. However, at the protein level, conventional immunohistochemistry (IHC) is limited to analyzing a specific protein at a time, whereas untargeted proteomic analysis offers a complementary approach to IHC, revealing potential insights into cancer biology and therapeutic targets.

Methods

Paired tumor and adjacent normal tissue samples were collected from 17 breast cancer patients with invasive ductal carcinoma staged I or II. Nanoflow liquid chromatography-high resolution mass spectrometry-based proteomic techniques and label-free quantitation were employed for protein profiling. The differences between tumor and adjacent normal portions were revealed by paired analysis, and the differences in the expression levels of tumor across samples were adjusted by the adjacent normal portions. Differentially expressed proteins (DEPs) were identified by at least 2-fold changes with p-values of paired t-test smaller than 0.05. The functional implications were explored using Gene Ontology (GO) analysis.

Results

More than eight thousand proteins were identified at a false discovery rate of 1 %, and 3,885 DEPs were found between tumor and adjacent normal tissues. GO analysis revealed that the tumor tissues were highlighted in the processes in gene expression, pathways related to cadherin binding, and functions involved in DNA repair, characterizing the cancerous nature in the alterations of focal adhesion, cellular motility, and the evolvement with genomic instability. Additionally, in the comparison of tumor tissues across patients, upregulations of programmed cell death and mismatch repair protein families were observed in some cases, implying potential benefits from immunotherapies.

Conclusion

This study demonstrates the value of untargeted proteomics in complementing IHC for comprehensive understanding of early-stage breast cancer. The proteins and pathways identified offer valuable insights into cancer biology and potentially improve diagnostic and therapeutic strategies.