Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer

• Published in: Oncotarget Vol. 9; no. 18; pp. 14193 - 14206
• Main Authors: Yamaguchi, Shigeo, Takahashi, Shin, Mogushi, Kaoru, Izumi, Yuki, Nozaki, Yumi, Nomizu, Tadashi, Kakugawa, Yoichiro, Ishida, Takanori, Ohuchi, Noriaki, Ishioka, Chikashi, Kato, Shunsuke
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 06.03.2018
• Subjects: Research Paper; breast cancer; prognostic biomarker; genomic instability; TP53; transcriptome
• DOI: 10.18632/oncotarget.24447
• ISSN: 1949-2553

signature has a robust predictive performance for prognosis in early-stage breast cancer, but the experiment that reported this relied on public microarray data and fresh-frozen samples. Before signature can be used in a clinical setting, a simple and low-cost diagnostic system using formalin-fixed paraffin-embedded (FFPE) samples is needed. New treatments based on the biological characteristics of signature are expected to follow. signature was evaluated in 174 FFPE early breast cancer specimens using digital quantification via the nCounter technique (NanoString). Patients were classified as signature mutant type ( = 64) or wild type ( = 110). Predictive power of signature was compared with those of other gene expression signatures in 153 fresh-frozen samples of the same cohort by RNA-seq. The molecular features of signature were elucidated using TCGA omics data and RNA-seq data to explore new therapeutic strategies for patients with signature mutant type. signature was a strong predictor of prognosis and was also more accurate than other gene expression signatures and independent of other clinicopathological factors. TCGA data analysis showed that risk score of signature was an index of chromosomal and genomic instability and that signature mutant type was associated with higher PD-L1 expression, variation in copy numbers, and numbers of somatic mutations. TP53 signature as diagnosed using the nCounter system is not only a robust predictor of prognosis but also a potential predictor of responsiveness to immune checkpoint inhibitors.