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Updated: Apr 28, 2026
Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Pathway-based analysis of breast cancer
Dong Song1, Miao Cui2, Gang Zhao1
1Department of Breast Surgery, The First Hospital, Jilin University Changchun, Jilin 130021, China.
Introduction:
Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer.
Methods:
13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array.
Results:
Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways.
Conclusions:
There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs.
Insights
Breast cancer involves broad pathway dysregulation at both mRNA and protein levels. Understanding these altered pathways can reveal new therapeutic targets beyond HER2 and ER pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Breast cancer pathogenesis involves more than just HER2 and ER pathways.
- Identifying additional altered pathways may lead to novel therapeutic strategies.
Purpose of the Study:
- To comprehensively analyze altered cancer pathway-related genes and proteins in breast cancer.
- To identify novel therapeutic targets by understanding pathway dysregulation.
Main Methods:
- Analyzed mRNA expression of 1243 cancer pathway genes in 13 invasive ductal carcinoma and 5 benign breast tissues using real-time PCR.
- Measured protein and phosphoprotein levels of 131 cancer pathway-related molecules in 33 paired breast cancer samples using a Protein Pathway Array.
Main Results:
- Significant differences in mRNA expression were observed between benign and cancer tissues, with some genes uniquely expressed in either.
- 57 proteins were significantly differentiated between tumor and normal tissues, with notable discrepancies between mRNA and protein expression.
- Pathway analysis revealed over 15 altered pathways, with p53, IL17, HGF, NGF, PTEN, and PI3K/AKT pathways shared between mRNA and protein data.
Conclusions:
- Breast cancer exhibits widespread pathway dysregulation at both mRNA and protein levels.
- mRNA expression levels do not consistently correlate with protein levels, indicating complex regulatory mechanisms.
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