TOMM40/FADS2 Expression Ratio Predicts the Sensitivity to mTOR Inhibitors in Triple-Negative Breast Cancer.

Authors

Salman Mohamed Farah, Jing-Quan Zheng, Leon Tsung-Ju Lee, Hsiao-Wei Lu, Wen-Ke Wang, Chia-Hao Kuei, Hui-Yu Lin, Hui-Wen Chiu, Yuan-Feng Lin

Published in

Cancer medicine. Volume 15. Issue 7. Pages e72089.

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). There is a lack of predictive biomarkers for the response of patients with TNBC to targeted therapies.
Bioinformatics analysis was conducted to generate differentially expressed genes (DEGs) of the mammalian target of rapamycin complex 1 (MTORC1) gene set between normal tissues and primary tumors derived from TNBC patients using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cox regression analysis was performed to identify independent prognostic factors. Endogenous expression levels of the identified prognostic genes were detected in a panel of TNBC cell lines and breast cancer tissues using western blotting and immunohistochemistry (IHC).
Our findings revealed two prognostic genes: FADS2 and TOMM40. TOMM40 (HR = 2.243) was a risk factor and FADS2 was a protective factor (HR = 0.652). A higher TOMM40/FADS2 ratio is associated with poor outcomes in patients with TNBC. The TOMM40/FADS2 ratio was significantly (p < 0.05) associated with age, tumor size, lymph node metastasis, pathologic stage, and overall survival of patients with TNBC. Remarkably, the MTT cytotoxicity assay revealed that TNBC cells, which possess a higher TOMM40/FADS2 ratio than TNBC cells with a lower TOMM40/FADS2 ratio, are more sensitive to mammalian target of rapamycin (mTOR) inhibitor treatment.
Our results provide a new therapeutic strategy using the TOMM40/FADS2 expression ratio to predict the cellular sensitivity to mTOR inhibitor treatment in TNBC.

PMID:
42470318
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.