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浸润性微乳头状癌和非特殊型乳腺癌细胞极性和细胞黏附相关基因表达差异及其预后意义。

Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance.

机构信息

2nd Department of Pathology, Semmelweis University, Üllői Street 93, Budapest, 1091, Hungary.

1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary.

出版信息

Sci Rep. 2021 Sep 16;11(1):18484. doi: 10.1038/s41598-021-97347-8.

DOI:10.1038/s41598-021-97347-8
PMID:34531452
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8446082/
Abstract

Invasive micropapillary carcinoma of the breast (IMPC) has been in the focus of several studies given its specific histology and clinicopathological course. We analysed mRNA expression profiles and the prognostic value of 43 genes involved in cell polarity, cell-adhesion and epithelial-mesenchymal transition (EMT) in IMPC tumors and compared them to invasive breast carcinomas of no special type (IBC-NST). IMPCs (36 cases), IBC-NSTs (36 cases) and mixed IMPC-IBC NSTs (8 cases) were investigated. mRNA expression level of selected genes were analysed using the NanoString nCounter Analysis System. Distant metastases free survival (DMFS) intervals were determined. Statistical analysis was performed using Statistica 13.5 software. Twelve genes showed significantly different expression in the IMPC group. There was no difference in DMFS according to histological type (IBC-NST vs. IMPC). High CLDN3, PALS1 and low PAR6 expression levels in the entire cohort were associated with shorter DMFS, and PALS1 was proven to be grade independent prognostic factor. Positive lymph node status was associated with higher levels of AKT1 expression. Differences in gene expression in IMPC versus IBC-NST may contribute to the unique histological appearance of IMPCs. No marked differences were observed in DMFS of the two groups. Altered gene expression in the mTOR signaling pathway in both tumor subtypes highlights the potential benefit from AKT/mTOR inhibitors in IMPCs similarly to IBC-NSTs.

摘要

乳腺浸润性微乳头状癌 (IMPC) 因其特殊的组织学和临床病理过程而成为多项研究的焦点。我们分析了 43 个涉及细胞极性、细胞黏附和上皮-间充质转化 (EMT) 的基因在 IMPC 肿瘤中的 mRNA 表达谱及其预后价值,并将其与非特殊型浸润性乳腺癌 (IBC-NST) 进行了比较。研究了 IMPC(36 例)、IBC-NST(36 例)和混合 IMPC-IBC NST(8 例)。使用 NanoString nCounter 分析系统分析选定基因的 mRNA 表达水平。确定无远处转移生存 (DMFS) 间隔。使用 Statistica 13.5 软件进行统计分析。在 IMPC 组中有 12 个基因的表达水平存在显著差异。根据组织学类型(IBC-NST 与 IMPC),DMFS 无差异。整个队列中 CLDN3、PALS1 高表达和 PAR6 低表达与较短的 DMFS 相关,并且 PALS1 被证明是独立于分级的预后因素。阳性淋巴结状态与 AKT1 表达水平升高相关。IMPC 与 IBC-NST 之间基因表达的差异可能有助于 IMPC 的独特组织学表现。两组之间的 DMFS 无明显差异。两种肿瘤亚型中 mTOR 信号通路中基因表达的改变突出了 AKT/mTOR 抑制剂在 IMPC 中的潜在获益,与 IBC-NST 相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/970c71da92a5/41598_2021_97347_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/3fc8fdb19be4/41598_2021_97347_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/778e56982d99/41598_2021_97347_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/c1c0fef1e216/41598_2021_97347_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/0ca52e7a7210/41598_2021_97347_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/7a6c5d07614d/41598_2021_97347_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/970c71da92a5/41598_2021_97347_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/3fc8fdb19be4/41598_2021_97347_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/778e56982d99/41598_2021_97347_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/c1c0fef1e216/41598_2021_97347_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/0ca52e7a7210/41598_2021_97347_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/7a6c5d07614d/41598_2021_97347_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4639/8446082/970c71da92a5/41598_2021_97347_Fig6_HTML.jpg

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