Eiji Suzuki1, Masahiro Sugimoto2, Kosuke Kawaguchi3, Fengling Pu3, Ryuji Uozumi4, Ayane Yamaguchi3, Mariko Nishie3, Moe Tsuda3, Takeshi Kotake3, Satoshi Morita4, Masakazu Toi3. 1. Breast Surgery Department, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. eijis@kuhp.kyoto-u.ac.jp. 2. Health Promotion and Preemptive Medicine, Research and Development Center for Minimally Invasive Therapies, Tokyo Medical University, 6-1-1 Shinjuku, Tokyo, Japan. 3. Breast Surgery Department, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. 4. Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
Abstract
BACKGROUND: It has been reported that the gene expression profile of peripheral blood mononuclear cells (PBMCs) exhibits a unique gene expression signature in several types of cancer. In this study, we aimed to explore the breast cancer patient-specific gene expression profile of PBMCs and discuss immunological insight on host antitumor immune responses. METHODS: We comprehensively analyzed the gene expression of PBMCs by RNA sequencing in the breast cancer patients as compared to that of healthy volunteers (HVs). Pathway enrichment analysis was performed on MetaCoretm to search the molecular pathways associated with the gene expression profile of PBMCs in cancer patients compared with HVs. RESULTS: We found a significant unique gene expression signature, such as the Toll-like receptor (TLR) 3- and TLR4-induced Toll/interleukin-1 receptor domain-containing adapter molecule 1 (TICAM1)-specific signaling pathway in the breast cancer patients as compared to that of healthy volunteers. Distinctive immunological gene expression profiles also showed the possibility of classifying breast cancer patients into subgroups such as T-cell inhibitory and monocyte-activating groups independent of known phenotypes of breast cancer. CONCLUSIONS: These preliminary findings suggest that evaluation of gene expression patterns of PBMCs might be both a less invasive diagnostic procedure and a useful way to reveal immunological insight of breast cancer, including biomarkers for cancer immunotherapy, such as immune checkpoint inhibitor therapy.
BACKGROUND: It has been reported that the gene expression profile of peripheral blood mononuclear cells (PBMCs) exhibits a unique gene expression signature in several types of cancer. In this study, we aimed to explore the breast cancerpatient-specific gene expression profile of PBMCs and discuss immunological insight on host antitumor immune responses. METHODS: We comprehensively analyzed the gene expression of PBMCs by RNA sequencing in the breast cancerpatients as compared to that of healthy volunteers (HVs). Pathway enrichment analysis was performed on MetaCoretm to search the molecular pathways associated with the gene expression profile of PBMCs in cancerpatients compared with HVs. RESULTS: We found a significant unique gene expression signature, such as the Toll-like receptor (TLR) 3- and TLR4-induced Toll/interleukin-1 receptor domain-containing adapter molecule 1 (TICAM1)-specific signaling pathway in the breast cancerpatients as compared to that of healthy volunteers. Distinctive immunological gene expression profiles also showed the possibility of classifying breast cancerpatients into subgroups such as T-cell inhibitory and monocyte-activating groups independent of known phenotypes of breast cancer. CONCLUSIONS: These preliminary findings suggest that evaluation of gene expression patterns of PBMCs might be both a less invasive diagnostic procedure and a useful way to reveal immunological insight of breast cancer, including biomarkers for cancer immunotherapy, such as immune checkpoint inhibitor therapy.
Authors: Saurabh K Garg; Eric A Welsh; Bin Fang; Yuliana I Hernandez; Trevor Rose; Jhanelle Gray; John M Koomen; Anders Berglund; James J Mulé; Joseph Markowitz Journal: Cancers (Basel) Date: 2020-11-26 Impact factor: 6.639