Author:
Yan Yiqing,Li Lun,Wang Zixin,Pang Jian,Guan Xinyu,Yuan Yunchang,Xia Zhenkun,Yi Wenjun
Abstract
AbstractTo explore the clinical role of QPRT in breast cancer. The gene expression, methylation levels and prognostic value of QPRT in breast cancer was analyzed using TCGA data. Validation was performed using the data from GEO dataset and TNMPLOT database. Meta analysis method was used to pool the survival data for QPRT. The predictive values of QPRT for different drugs were retrieved from the ROC plot. The expression differences of QPRT in acquired drug-resistant and sensitive cell lines were analyzed using GEO datasets. GO and KEGG enrichment analysis were conducted for those genes which were highly co-expressed with QPRT in tissue based on TCGA data and which changed after QPRT knockdown. Timer2.0 was utilized to explore the correlation between QPRT and immune cells infiltration, and the Human Protein Atlas was used to analyse QPRT’s single-cell sequencing data across different human tissues. The expression of QPRT in different types of macrophages, and the expression of QPRT were analysed after coculturing HER2+ breast cancer cells with macrophages. Additionally, TargetScan, Comparative Toxicogenomics and the connectivity map were used to research miRNAs and drugs that could regulate QPRT expression. Cytoscape was used to map the interaction networks between QPRT and other proteins. QPRT was highly expressed in breast cancer tissue and highly expressed in HER2+ breast cancer patients (P < 0.01). High QPRT expression levels were associated with worse OS, DMFS, and RFS (P < 0.01). Two sites (cg02640602 and cg06453916) were found to be potential regulators of breast cancer (P < 0.01). QPRT might predict survival benefits in breast cancer patients who received taxane or anthracycline. QPRT was associated with tumour immunity, especially in macrophages. QPRT may influence the occurrence and progression of breast cancer through the PI3K-AKT signalling pathway, Wnt signalling pathway, and cell cycle-related molecules.
Funder
the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University
the Guangdong Provincial Laboratory of Advanced Energy Science and Technology
the Natural Science Foundation of Hunan Province of China
the Science and Technology Innovation Program of Hunan Province
the Health and Family Planning Commission of Hunan Province
the Tumor clinical research of Public welfare of Xiaoxiang
the Graduate Research and Innovation Projects of Hunan Province of China
Publisher
Springer Science and Business Media LLC
Reference64 articles.
1. Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: Cancer J. Clin. 71(3), 209–249 (2021).
2. Yersal, O. & Barutca, S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J. Clin. Oncol. 5(3), 412–424 (2014).
3. Emens, L. A. Breast cancer immunotherapy: Facts and hopes. Clin. Cancer Res.: Off. J. Am. Assoc. Cancer Res. 24(3), 511–520 (2018).
4. Prat, A. et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast (Edinburgh, Scotland). 24(Suppl 2), S26-35 (2015).
5. Bredin, P., Walshe, J. M. & Denduluri, N. Systemic therapy for metastatic HER2-positive breast cancer. Semin. Oncol. 47(5), 259–269 (2020).