ساخت اکانت کاربری رایگان

مقالات پذیرفته شده کنگره

  • صفحه نخست
  • مقالات پذیرفته شده اولین کنگره بین المللی ژنتیک سرطان
بازنشر

  • Transcriptomic and PPI Network Analysis Reveals Hub Genes in Breast Cancer-Associated Fibroblasts

  • Fatemeh Kazemzadeh,1 Zahra Sadat Tabatabaei,2 Razieh Heidari,3 Seyed Abbas Mirzaei,4,*
    1. Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
    2. Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
    3. Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
    4. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.


  • Introduction: Cancer-associated fibroblasts (CAFs) are major components of the breast tumor microenvironment and contribute to tumor progression through interactions with cancer cells and remodeling of the tumor stroma. Increasing evidence indicates that CAFs are molecularly and functionally heterogeneous. However, the transcriptional alterations that distinguish breast CAFs from normal breast fibroblasts remain incompletely characterized. In particular, the contribution of cell-cycle, chromosomal organization, epigenetic regulation, and DNA-repair programs to the molecular phenotype of CAFs requires further investigation.
  • Methods: The publicly available microarray dataset GSE29270, entitled “Molecular Characterization of Breast Carcinoma Associated Fibroblasts,” was analyzed to compare gene expression profiles between breast cancer-associated fibroblasts and normal breast fibroblasts. Following preprocessing and normalization, differential expression analysis was performed using the LIMMA package. Differentially expressed genes (DEGs) were defined using an adjusted q-value < 0.05 and |log2 fold change| > 0.5. Sample expression distributions and differential expression patterns were evaluated using box plot and volcano plot analyses, respectively (Figures 1 and 2). The identified DEGs were subsequently used to construct a protein–protein interaction (PPI) network (Figure 3). Hub genes were prioritized using the cytoHubba plugin and Maximal Clique Centrality (MCC) algorithm, and the top hub genes were visualized within the PPI network (Figure 4).
  • Results: Approximately 300 DEGs were identified between CAFs and normal breast fibroblasts. PPI analysis demonstrated extensive interactions among the identified DEGs. MCC analysis identified 10 hub genes, including NCAPH, PLK1, ASPM, SPAG5, CENPE, NCAPG2, HDAC1, RAD21, MSH2, and MSH6. Notably, NCAPH was upregulated, whereas the other nine hub genes were downregulated in CAFs. Functionally, these hub genes were predominantly associated with cell-cycle regulation, mitotic progression, chromosome organization and segregation, chromatin regulation, and DNA mismatch repair. The coordinated downregulation of several mitosis-associated genes, including PLK1, ASPM, SPAG5, CENPE, and NCAPG2, is noteworthy because previous studies have identified proliferative CAF subpopulations characterized by increased expression of cell-cycle-related genes. This difference may reflect the molecular heterogeneity of CAF populations and suggests that the CAFs represented in GSE29270 may not exhibit a uniformly proliferative phenotype. Furthermore, the identification of these genes as network hubs indicates high topological connectivity but does not establish a direct causal role in CAF activation.
  • Conclusion: The present study identified a distinct hub-gene network associated with breast cancer-associated fibroblasts and revealed coordinated alterations in genes involved in cell-cycle regulation, mitosis, chromosome organization, chromatin regulation, and DNA repair. The contrasting pattern of NCAPH upregulation and broad downregulation of other mitotic and genome-maintenance hub genes suggests remodeling of cellular and genomic regulatory programs rather than a simple increase in CAF proliferation. These findings are consistent with the recognized heterogeneity of CAF states and provide candidate molecular regulators for further functional investigation. Experimental validation of the identified hub genes, particularly NCAPH, is warranted to determine their specific contribution to CAF biology and breast cancer progression.
  • Keywords: Cancer-associated fibroblasts; Breast cancer; Hub genes; Cell cycle; DNA repair

به خانواده بزرگ کنسر ژنتیکس و ژنومیکس سرطان بپیوندید!

ایجاد حساب کاربری رایگان