Department of Clinical Medical Research Center, Inner Mongolia People's Hospital, Hohhot, 010010, China.
Department of Oncology, Inner Mongolia People's Hospital, Hohhot, 010010, China.
Biochem Genet. 2023 Aug;61(4):1282-1299. doi: 10.1007/s10528-022-10317-1. Epub 2022 Dec 22.
Autophagy is closely related to breast cancer and has the dual role of promoting and inhibiting the progression of breast cancer. In this study, we aimed to establish an autophagy-related gene signature for the prognosis of breast cancer. A gene signature composed of the eight most survival-relevant autophagy-associated genes was identified by least absolute shrinkage and selection operator (LASSO) regression analysis. A risk score was calculated based on the gene signature, which divided breast cancer patients into low- or high-risk groups and showed good and poor prognosis, respectively. The risk score displayed good prognostic performance in both the training cohort (TCGA, 1-10-year AUC > 0.63) and the validation cohort (GEO, 1-10-year AUC > 0.66). The multivariate Cox regression and stratified analysis revealed that the risk score was an independent prognostic factor for breast cancer patients. Moreover, the high-risk score was associated with higher infiltration of neutrophils and M2-polarized macrophages, and lower infiltration of resting memory CD4 T cells, CD8 T cells, and NK cells. Finally, the high-risk score was associated with myc target, glycolysis, and mTORC1 signaling. The risk score developed based on the autophagy-associated gene signature was an independent prognostic biomarker for breast cancer.
自噬与乳腺癌密切相关，具有促进和抑制乳腺癌进展的双重作用。本研究旨在建立自噬相关基因特征，用于预测乳腺癌的预后。通过最小绝对值收缩和选择算子（LASSO）回归分析，确定了由 8 个与生存最相关的自噬相关基因组成的基因特征。基于基因特征计算风险评分，将乳腺癌患者分为低风险或高风险组，分别显示出良好和较差的预后。该风险评分在训练队列（TCGA，1-10 年 AUC>0.63）和验证队列（GEO，1-10 年 AUC>0.66）中均表现出良好的预后性能。多变量 Cox 回归和分层分析表明，风险评分是乳腺癌患者的独立预后因素。此外，高风险评分与中性粒细胞和 M2 极化巨噬细胞浸润增加，以及静止记忆 CD4 T 细胞、CD8 T 细胞和 NK 细胞浸润减少相关。最后，高风险评分与 myc 靶标、糖酵解和 mTORC1 信号有关。基于自噬相关基因特征建立的风险评分是乳腺癌的独立预后生物标志物。
