# Identifying Molecular Determinants and Therapeutic Targets in Luminal B Breast Cancer: A Systems Biology Approach

**Authors:** Yousef Saeidi, Masoud Ghorbani, Ali Najafi, Mehrdad Moosazadeh Moghaddam

PMC · DOI: 10.30699/ijp.2025.2067802.3499 · Iranian Journal of Pathology · 2025-08-15

## TL;DR

This study uses systems biology to identify key genes and pathways in Luminal B breast cancer, aiming to improve diagnosis and treatment.

## Contribution

The study identifies novel hub genes, transcription factors, and miRNAs specific to Luminal B breast cancer using systems biology approaches.

## Key findings

- Top hub genes in LBBC include FGF2, EGFR, and MET, among others.
- Key transcription factors identified include RELA, PPARG, and CTCF.
- Potential biomarkers include CDK1, CDK2, and MAPK3.

## Abstract

Luminal B breast cancer (LBBC) is on the rise worldwide, with both incidence and mortality rates steadily increasing. Early detection proves difficult due to its aggressive characteristics, most notably its heightened proliferation rate and the complex interplay of molecular biomarkers, particularly in more advanced stages.

Data Sources: In the present study, we conducted an in-silico analysis of LBBC cell lines using the Gene Expression Omnibus (GEO) microarray dataset, which includes 30 LBBC and 11 normal samples. Analysis Tools: Differentially expressed genes (DEGs) were identified using RStudio. A series of analyses, including cancer data interrogation via pan-cancer analysis, eXpression2Kinases (X2K), and the Cancer Dependency Map (DepMAP), was carried out to elucidate the underlying signaling pathways, transcription factors (TFs), and kinases, as well as to perform stemformatics analysis. Protein–protein interaction (PPI) networks were reconstructed using STRING and Cytoscape, enabling the identification of co-expressed and hub genes through the cytoHubba plug-in.

Of notes, FGF2, EGFR, ADIPOQ, LIPE, MET, IGF1, FGF1, EGF, FGF7, and PPARG were identified as the top 10 hub genes; RELA, PPARG, CTCF, EGR1, and NFE2L2 were detected as predominant TFs in LBBC; and CDK1, CDK2, MAPK3, CSNK2A1, and MAPK14 were identified as potential biomarkers through hub gene clustering. Further analysis indicated hsa-mir-221-3p and hsa-mir-29a-3p as key miRNAs targeting LBBC-related genes.

Collectively, our findings highlighted LBBC-associated genes, TFs, miRNAs, and pathways as prospective biomarkers, providing insights into LBBC diagnosis and therapeutic approaches.

## Linked entities

- **Genes:** FGF2 (fibroblast growth factor 2) [NCBI Gene 2247], EGFR (epidermal growth factor receptor) [NCBI Gene 1956], ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370], LIPE (lipase E, hormone sensitive type) [NCBI Gene 3991], MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233], IGF1 (insulin like growth factor 1) [NCBI Gene 3479], FGF1 (fibroblast growth factor 1) [NCBI Gene 2246], EGF (epidermal growth factor) [NCBI Gene 1950], FGF7 (fibroblast growth factor 7) [NCBI Gene 2252], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970], CTCF (CCCTC-binding factor) [NCBI Gene 10664], EGR1 (early growth response 1) [NCBI Gene 1958], NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780], CDK1 (cyclin dependent kinase 1) [NCBI Gene 983], CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017], MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595], CSNK2A1 (casein kinase 2 alpha 1) [NCBI Gene 1457], MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, CSNK2A1 (casein kinase 2 alpha 1) [NCBI Gene 1457] {aka CK2A1, CKII, Cka1, Cka2, OCNDS}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, FGF1 (fibroblast growth factor 1) [NCBI Gene 2246] {aka AFGF, ECGF, ECGF-beta, ECGFA, ECGFB, FGF-1}, CTCF (CCCTC-binding factor) [NCBI Gene 10664] {aka CFAP108, FAP108, MRD21}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, LIPE (lipase E, hormone sensitive type) [NCBI Gene 3991] {aka AOMS4, FPLD6, HSL, LHS, REH}, CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, FGF7 (fibroblast growth factor 7) [NCBI Gene 2252] {aka HBGF-7, KGF}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}
- **Diseases:** Cancer (MESH:D009369), LBBC (MESH:D001943)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12520586/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12520586/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12520586/full.md

---
Source: https://tomesphere.com/paper/PMC12520586