Dataset Information

Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

ABSTRACT: Regulatory CD4+ T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) were analyzed. Treg abundance was not associated with cancer aggressiveness, patient survival, or immune activity markers, but it was lower in metastatic tumors when compared to matched primary tumors. Treg was associated with a high mutation rate of TP53 genes and copy number mutations as well as with increased tumor infiltration of M2 macrophages and decreased infiltration of T helper type 1 (Th1) cells. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) was significantly associated with low Treg abundance in triple negative breast cancer (TNBC) but not in ER-positive/Her2-negative subtype. High Treg abundance was significantly associated with high tumor expression of multiple immune checkpoint inhibitor genes. In conclusion, Treg abundance may have potential as a predictive biomarker of pCR after NAC in TNBC.

SUBMITTER: Oshi M

PROVIDER: S-EPMC7603157 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Oshi Masanori M Asaoka Mariko M Tokumaru Yoshihisa Y Angarita Fernando A FA Yan Li L Matsuyama Ryusei R Zsiros Emese E Ishikawa Takashi T Endo Itaru I Takabe Kazuaki K

Cancers 20201019 10

Regulatory CD4<sup>+</sup> T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) wer ...[more]

PMID: 33086518

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Project description:Due to the positive association between neoadjuvant chemotherapy (NACT) and the promising early response rates of patients with triple negative breast cancer (TNBC), including probabilities of pathological complete response, NACT is increasingly used in TNBC management. Liquid biopsy‑based biomarkers with the power to diagnose the early response to NACT may support established monitoring tools, which are to a certain extent imprecise and costly. Simple serum‑ or urine‑based analyses of non‑coding RNA (ncRNA) expression may allow for fast, minimally‑invasive testing and timely adjustment of the therapy regimen. The present study investigated breast cancer‑related ncRNAs [microRNA (miR)‑7, ‑9, ‑15a, ‑17, ‑18a, ‑19b, ‑21, ‑30b, ‑222 and ‑320c, PIWI‑interacting RNA‑36743 and GlyCCC2] in triple positive BT‑474 cells and three TNBC cell lines (BT‑20, HS‑578T and MDA‑MB‑231) treated with various chemotherapeutic agents using reverse transcription‑quantitative PCR. Intracellular and secreted microvesicular ncRNA expression levels were analysed using a multivariable statistical regression analysis. Chemotherapy‑driven effects were investigated by analysing cell cycle determinants at the mRNA and protein levels. Serum and urine specimens from 8 patients with TNBC were compared with 10 healthy females using two‑sample t‑tests. Samples from the patients with TNBC were compared at two time points. Chemotherapeutic treatments induced distinct changes in ncRNA expression in TNBC cell lines and the BT‑474 cell line in intra‑ and extracellular compartments. Serum and urine‑based ncRNA expression analysis was able to discriminate between patients with TNBC and controls. Time point comparisons in the urine samples of patients with TNBC revealed a general rise in the level of ncRNA. Serum data suggested a potential association between piR‑36743, miR‑17, ‑19b and ‑30b expression levels and an NACT‑driven complete clinical response. The present study highlighted the potential of ncRNAs as liquid biopsy‑based biomarkers in TNBC chemotherapy treatment. The ncRNAs tested in the present study have been previously investigated for their involvement in BC or TNBC chemotherapy responses; however, these previous studies were restricted to patient tissue or in vitro models. The data from the present study offer novel insight into ncRNA expression in liquid samples from patients with TNBC, and the study serves as an initial step in the evaluation of ncRNAs as diagnostic biomarkers in the monitoring of TNBC therapy.

Dataset Information

Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Publications

Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

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