Characterization of starvation response-related genes for predicting prognosis in breast cancer

作者全名："Wang, Yuan; Gao, Shun; Xu, Yingkun; Tang, Zhenrong; Liu, Shengchun"

作者地址："[Wang, Yuan; Gao, Shun; Xu, Yingkun; Tang, Zhenrong; Liu, Shengchun] Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing, Peoples R China; [Wang, Yuan; Gao, Shun] Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing, Peoples R China"

通信作者："Liu, SC (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing, Peoples R China."

来源：CANCER SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000991501800001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：breast cancer; EIF2AK3; mRNA signature; prognostic prediction; starvation response

摘要："Breast cancer (BRCA) cells typically exist in nutrient-deficient microenvironments and quickly adapt to states with fluctuating nutrient levels. The tumor microenvironment of starvation is intensely related to metabolism and the malignant progression of BRCA. However, the potential molecular mechanism has not been thoroughly scrutinized. As a result, this study aimed to dissect the prognostic implications of mRNAs involved in the starvation response and construct a signature for forecasting the outcomes of BRCA. In this research, we investigated how starvation could affect BRCA cells' propensities for invasion and migration. The effects of autophagy and glucose metabolism mediated by starved stimulation were examined through transwell assays, western blot, and the detection of glucose concentration. A starvation response-related gene (SRRG) signature was ultimately generated by integrated analysis. The risk score was recognized as an independent risk indicator. The nomogram and calibration curves revealed that the model had excellent prediction accuracy. Functional enrichment analysis indicated this signature was significantly enriched in metabolic-related pathways and energy stress-related biological processes. Furthermore, phosphorylated protein expression of the model core gene EIF2AK3 increased after the stimulus of starvation, and EIF2AK3 may play an essential role in the progression of BRCA in the starved microenvironment. To sum up, we constructed and validated a novel SRRG signature that could accurately predict outcomes and may be developed as a therapeutic target for the precise treatment of BRCA."

基金机构：Doctoral Research Innovation Project of the First Affiliated Hospital of Chongqing Medical University [CYYY- BSYJSCXXM-202213]; National Natural Science Foundation of China [81772979]

基金资助正文："Doctoral Research Innovation Project of the First Affiliated Hospital of Chongqing Medical University, Grant/Award Number: CYYY- BSYJSCXXM-202213; National Natural Science Foundation of China, Grant/Award Number: 81772979"