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SCD5 表达与乳腺癌的预后和新辅助化疗反应相关。

SCD5 expression correlates with prognosis and response to neoadjuvant chemotherapy in breast cancer.

机构信息

Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.

Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, 300387, People's Republic of China.

出版信息

Sci Rep. 2021 Apr 26;11(1):8976. doi: 10.1038/s41598-021-88258-9.

Abstract

Neoadjuvant chemotherapy (NACT) represents a standard option for breast cancer. Unfortunately, about 55-80% of breast cancer patients do not have a favorable response to chemotherapy. Highly specific tumor biomarker that can predict the pathological response to neoadjuvant chemotherapy is lacking. Stearoyl-CoA desaturase 5 (SCD5) is an integral membrane protein of the endoplasmic reticulum that participates in lipid metabolism. Previous studies on the role of SCD5 in human cancers drew different conclusions. Therefore, the role of SCD5 in breast cancer remains unclear. Our study aims to understand its expression signature, prognosis value and correlation with pathological response to NACT in breast cancer using bioinformatics from public databases. Analysis of samples from public databases showed that SCD5 expression was down-regulated in some human cancers including breast cancer, and low expression of SCD5 was associated with more aggressive breast cancer phenotypes. Survival analysis revealed that SCD5 expression was related to prognosis in breast cancer. Integrated analysis of multiple public datasets indicated that SCD5 expression signature was associated with pathological response to NACT, particularly in TNBC. Based on functional enrichment analysis, the most affected biological functions in high SCD5-expressing breast cancer tissues were involved in negative regulation of cell cycle. Moreover, a significantly negative correlation between SCD5 expression and several cell cycle regulators was noted. Taken together, SCD5 was involved in the development and progression of breast cancer and might be a predictive biomarker for response to NACT. In conclusion, SCD5 could serve as a predictive biomarker of pathological response to NACT and play a carcinostatic role in breast cancer. These results provided us with clues to better understand SCD5 from the perspective of bioinformatics and highlighted the clinical importance of SCD5 in breast cancer, especially triple negative breast cancer (TNBC).

摘要

新辅助化疗(NACT)是乳腺癌的标准治疗选择。不幸的是,约 55-80%的乳腺癌患者对化疗反应不佳。缺乏能够预测新辅助化疗病理反应的高度特异性肿瘤生物标志物。硬脂酰辅酶 A 去饱和酶 5(SCD5)是内质网的一种完整膜蛋白,参与脂质代谢。之前关于 SCD5 在人类癌症中的作用的研究得出了不同的结论。因此,SCD5 在乳腺癌中的作用尚不清楚。我们的研究旨在通过公共数据库中的生物信息学方法,了解其表达谱、预后价值以及与乳腺癌对 NACT 的病理反应的相关性。对公共数据库样本的分析表明,SCD5 在一些人类癌症中表达下调,包括乳腺癌,并且 SCD5 低表达与更具侵袭性的乳腺癌表型相关。生存分析显示 SCD5 表达与乳腺癌的预后相关。多个公共数据集的综合分析表明,SCD5 表达谱与 NACT 的病理反应相关,尤其是在三阴性乳腺癌(TNBC)中。基于功能富集分析,在 SCD5 高表达的乳腺癌组织中受影响最严重的生物学功能涉及细胞周期的负调控。此外,还注意到 SCD5 表达与几种细胞周期调节剂之间存在显著的负相关。总之,SCD5 参与了乳腺癌的发生和发展,可能是预测对 NACT 反应的生物标志物。综上所述,SCD5 可以作为预测 NACT 病理反应的生物标志物,并在乳腺癌中发挥抗癌作用。这些结果为我们从生物信息学角度更好地理解 SCD5 提供了线索,并强调了 SCD5 在乳腺癌中的临床重要性,尤其是三阴性乳腺癌(TNBC)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b571/8076324/b3a5b277266c/41598_2021_88258_Fig1_HTML.jpg

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