Manara - Qatar Research Repository
4 files

Molecular subtyping and functional validation of TTK, TPX2, UBE2C, and LRP8 in sensitivity of TNBC to paclitaxel

journal contribution
submitted on 2024-05-22, 08:35 and posted on 2024-05-22, 08:36 authored by Ramesh Elango, Radhakrishnan Vishnubalaji, Hibah Shaath, Nehad M. Alajez

Triple-negative breast cancer (TNBC) patients exhibit variable responses to chemotherapy, suggesting an underlying molecular heterogeneity. In the current study, we analyzed publicly available transcriptome data from 360 TNBC and 88 normal breast tissues, which revealed activation of nucleosome and cell cycle as the hallmarks of TNBC. Mechanistic network analysis identified activation of FOXM1 and ERBB2, and suppression of TP53 and NURP1 networks in TNBC. Employing Iterative Clustering and Guide-gene Selection (ICGS), Uniform Manifold Approximation and Projection (UMAP), and dimensionality reduction analyses, we classified TNBC into seven molecular subtypes, each exhibiting a unique molecular signature, including immune infiltration (CD19, CD8, and macrophages) and mesenchymal signature, which correlated with variable disease outcomes in a larger cohort (1,070) of BC. Mechanistically, depletion of TTK, TPX2, UBE2C, CDCA7, MELK, NFE2L3, DDX39A, and LRP8 led to substantial inhibition of colony formation of TNBC models, which was further enhanced in the presence of paclitaxel. Our data provide novel insights into the molecular heterogeneity of TNBC and identified TTK, TPX2, UBE2C, and LRP8 as main drivers of TNBC tumorigenesis.

Other Information

Published in: Molecular Therapy - Methods & Clinical Development
See article on publisher's website:


Open Access funding provided by the Qatar National Library.



  • English



Publication Year

  • 2021

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI

Usage metrics

    Qatar Biomedical Research Institute - HBKU


    Ref. manager