Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy

Zhang, Wei; Li, Emma; Wang, Lily; Lehmann, Brian D.; Chen, X. Steven

doi:10.3390/cancers15082194

Cited by 3 publications

References 77 publications

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A phenocopy signature of TP53 loss predicts response to chemotherapy

Bakhtiar,

Sharifi,

Helzer

et al. 2024

npj Precis. Onc.

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In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.

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A phenocopy signature of TP53 loss predicts response to chemotherapy

Bakhtiar,

Sharifi,

Helzer

et al. 2024

npj Precis. Onc.

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Tumor-Infiltrating Lymphocytes Display Prognostic Signatures Associated with Chemotherapy Response in TNBC Patients

Banerjee,

Tiwari,

Raman

et al. 2024

Preprint

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Triple-negative breast cancer (TNBC) is an aggressive subtype often marked by resistance to neoadjuvant chemotherapy (NAC), making treatment particularly challenging. Tumor-infiltrating lymphocytes (TILs), crucial players in the immune landscape of tumors, have been associated with treatment outcomes, but the prognostic potential of TIL-derived gene markers in pre-NAC samples from TNBC patients remains understudied. In this research, we analyzed the single-cell transcriptional profiles of approximately 5,000 cells from four chemosensitive and four chemoresistant TNBC patients using publicly available datasets. Leveraging standard single-cell analysis, we identified differentially expressed gene signatures within the TIL subpopulation, highlighting significant immune activation pathways differentiating chemoresistant from chemosensitive tumors. By employing robust feature selection and repeated cross-validation across microarray and RNA-seq datasets, we developed a stable set of 30 TIL-based gene markers with notable prognostic relevance for NAC response in TNBC. These markers achieved an AUROC of 0.78 in the training set and validated with AUROCs of 0.8, 0.658, and 0.736 across five independent test datasets, demonstrating consistency across diverse platforms and sequencing technologies. Furthermore, increased expression of these gene signatures correlated with improved recurrence-free survival (RFS) in a cohort of 220 TNBC patients. This study enhances our understanding of the TIL transcriptional landscape in NAC response, identifying potential biomarkers and therapeutic targets for improving treatment outcomes in TNBC.

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Multi‐omic analysis of dysregulated pathways in triple negative breast cancer

Sajjad,

Jalal,

Jalal

et al. 2024

Asia-Pac J Clncl Oncology

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The aggressive characteristics of triple‐negative breast cancer (TNBC) and the absence of targeted medicines make TNBC a challenging clinical case. The molecular landscape of TNBC has been well‐understood thanks to recent developments in multi‐omic analysis, which have also revealed dysregulated pathways and possible treatment targets. This review summarizes the utilization of multi‐omic approaches in elucidating TNBC's complex biology and therapeutic avenues. Dysregulated pathways including cell cycle progression, immunological modulation, and DNA damage response have been uncovered in TNBC by multi‐omic investigations that integrate genomes, transcriptomics, proteomics, and metabolomics data. Methods like this pave the door for the discovery of new therapeutic targets, such as the EGFR, PARP, and mTOR pathways, which in turn direct the creation of more precise treatments. Recent developments in TNBC treatment strategies, including immunotherapy, PARP inhibitors, and antibody‐drug conjugates, show promise in clinical trials. Emerging biomarkers like MUC1, YB‐1, and immune‐related markers offer insights into personalized treatment approaches and prognosis prediction. Despite the strengths of multi‐omic analysis in offering a more comprehensive view and personalized treatment strategies, challenges exist. Large sample sizes and ensuring high‐quality data remain crucial for reliable findings. Multi‐omic analysis has revolutionized TNBC research, shedding light on dysregulated pathways, potential targets, and emerging biomarkers. Continued research efforts are imperative to translate these insights into improved outcomes for TNBC patients.

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Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy

Cited by 3 publications

References 77 publications

A phenocopy signature of TP53 loss predicts response to chemotherapy

A phenocopy signature of TP53 loss predicts response to chemotherapy

Tumor-Infiltrating Lymphocytes Display Prognostic Signatures Associated with Chemotherapy Response in TNBC Patients

Multi‐omic analysis of dysregulated pathways in triple negative breast cancer

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