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CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients
Authors:Jianguo Lai  Xiaoyi Lin  Fangrong Cao  Hsiaopei Mok  Bo Chen  Ning Liao
Affiliation:1. Department of Breast Cancer, Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences, Guangzhou, China;2. Department of Breast Cancer, Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences, Guangzhou, China

Contribution: Formal analysis (lead), ​Investigation (lead), Supervision (lead);3. Department of Breast Cancer, Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences, Guangzhou, China

Contribution: Data curation (lead), ​Investigation (lead), Resources (lead), Software (lead), Visualization (lead);4. Department of Breast Cancer, Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences, Guangzhou, China

Contribution: Data curation (lead), Resources (lead), Software (lead)

Abstract:Breast cancer (BC) prognosis and therapeutic sensitivity could not be predicted efficiently. Previous evidence have shown the vital roles of CDKN1C in BC. Therefore, we aimed to construct a CDKN1C-based model to accurately predicting overall survival (OS) and treatment responses in BC patients. In this study, 995 BC patients from The Cancer Genome Atlas database were selected. Kaplan-Meier curve, Gene set enrichment and immune infiltrates analyses were executed. We developed a novel CDKN1C-based nomogram to predict the OS, verified by the time-dependent receiver operating characteristic curve, calibration curve and decision curve. Therapeutic response prediction was followed based on the low- and high-nomogram score groups. Our results indicated that low-CDKN1C expression was associated with shorter OS and lower proportion of naïve B cells, CD8 T cells, activated NK cells. The predictive accuracy of the nomogram for 5-year OS was superior to the tumour-node-metastasis stage (area under the curve: 0.746 vs. 0.634, p < 0.001). The nomogram exhibited excellent predictive performance, calibration ability and clinical utility. Moreover, low-risk patients were identified with stronger sensitivity to therapeutic agents. This tool can improve BC prognosis and therapeutic responses prediction, thus guiding individualized treatment decisions.
Keywords:breast cancer  CDKN1C  overall survival  prognosis  therapeutic response
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