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表达与血管生成相关,是青少年及年轻成人(AYA)乳腺癌的预后生物标志物。

Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA).

作者信息

Oshi Masanori, Ziazadeh Danya, Wu Rongrong, Chida Kohei, Yamada Akimitsu, Yamamoto Shinya, Narui Kazutaka, Yan Li, Ishikawa Takashi, Endo Itaru, Takabe Kazuaki

机构信息

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

出版信息

Cancers (Basel). 2023 Jul 4;15(13):3489. doi: 10.3390/cancers15133489.

Abstract

It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest expression compared to ER-positive/HER2-negative BC, levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high- expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in expression levels among AYAs and older patients. However, high expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high expression demonstrated low levels of CD8 T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.

摘要

众所周知,青少年及年轻成人(AYA)群体与老年患者的基因信息存在差异。尽管已经开展了多项关于基因信息的研究,但目前尚无预后生物标志物可用于区分AYA患者的生存结局。GALNT基因家族与多种癌症病因相关,如Tn抗原和上皮-间质转化(EMT);然而,其在乳腺癌(BC)中的表达的临床意义仍不清楚。我们使用两个大型独立队列研究了其在BC中的表达的临床相关性。我们发现,尽管三阴性乳腺癌(TNBC)与雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌相比具有最高的表达,但在METABRIC和GSE96058队列中,BC中的水平与临床侵袭性(包括组织学分级、美国癌症联合委员会分期和N分类)以及患者生存率均无关联。通过基因集富集分析(GSEA)的标志性基因集分析,低表达和高表达的BC之间也没有生物学差异。此外,在AYA患者和老年患者中,表达水平未发现显著差异。然而,在两个队列中,高表达与AYA患者的生存率显著较差相关。此外,在AYA患者中,高表达被发现是包括亚型、组织学分级、美国癌症联合委员会T和N分类在内的多种临床特征中的独立因素。在两个队列中,高表达的BC显示出低水平的CD8 T细胞浸润,但其他抗癌或促癌免疫细胞则不然。最后,高表达的BC在AYA群体中显示出EMT、血管生成和蛋白质分泌增加,但在老年患者中则不然。总之,我们的研究结果表明,表达与血管生成和EMT相关,并且可能具有作为预后生物标志物的潜力,特别是在AYA患者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5a3/10341315/1ca56f5a35ed/cancers-15-03489-g001.jpg

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