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聚焦转录因子和共转录因子的肺小细胞癌综合免疫组织化学研究

Integrated Immunohistochemical Study on Small-Cell Carcinoma of the Lung Focusing on Transcription and Co-Transcription Factors.

作者信息

Sato Younosuke, Okamoto Isamu, Kameyama Hiroki, Kudoh Shinji, Saito Haruki, Sanada Mune, Kudo Noritaka, Wakimoto Joeji, Fujino Kosuke, Ikematsu Yuki, Tanaka Kentaro, Nishikawa Ayako, Sakaguchi Ryo, Ito Takaaki

机构信息

Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

出版信息

Diagnostics (Basel). 2020 Nov 13;10(11):949. doi: 10.3390/diagnostics10110949.

DOI:10.3390/diagnostics10110949
PMID:33202998
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7697657/
Abstract

Small-cell lung cancer (SCLC) is an aggressive malignant cancer that is classified into four subtypes based on the expression of the following key transcription and co-transcription factors: ASCL1, NEUROD1, YAP1, and POU2F3. The protein expression levels of these key molecules may be important for the formation of SCLC characteristics in a molecular subtype-specific manner. We expect that immunohistochemistry (IHC) of these molecules may facilitate the diagnosis of the specific SCLC molecular subtype and aid in the appropriate selection of individualized treatments. We attempted IHC of the four key factors and 26 candidate SCLC target molecules selected from the gene expression omnibus datasets of 47 SCLC samples, which were grouped based on positive or negative results for the four key molecules. We examined differences in the expression levels of the candidate targets and key molecules. ASCL1 showed the highest positive rate in SCLC samples, and significant differences were observed in the expression levels of some target molecules between the ASCL1-positive and ASCL1-negative groups. Furthermore, the four key molecules were coordinately and simultaneously expressed in SCLC cells. An IHC study of ASCL1-positive samples showed many candidate SCLC target molecules, and IHC could become an essential method for determining SCLC molecular subtypes.

摘要

小细胞肺癌(SCLC)是一种侵袭性恶性肿瘤,根据以下关键转录因子和共转录因子的表达分为四种亚型:ASCL1、NEUROD1、YAP1和POU2F3。这些关键分子的蛋白表达水平可能以分子亚型特异性方式对SCLC特征的形成很重要。我们期望对这些分子进行免疫组织化学(IHC)检测可能有助于SCLC特定分子亚型的诊断,并有助于适当选择个体化治疗方案。我们尝试对从47个SCLC样本的基因表达综合数据集中选出的四个关键因子和26个候选SCLC靶分子进行IHC检测,这些样本根据四个关键分子的阳性或阴性结果进行分组。我们检查了候选靶标和关键分子表达水平的差异。ASCL1在SCLC样本中显示出最高的阳性率,并且在ASCL1阳性组和ASCL1阴性组之间观察到一些靶分子表达水平的显著差异。此外,这四个关键分子在SCLC细胞中协同且同时表达。对ASCL1阳性样本的IHC研究显示出许多候选SCLC靶分子,并且IHC可能成为确定SCLC分子亚型的重要方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/c656bc433343/diagnostics-10-00949-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/d13e8b154d91/diagnostics-10-00949-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/f1fb8f6a2e7b/diagnostics-10-00949-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/c656bc433343/diagnostics-10-00949-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/d13e8b154d91/diagnostics-10-00949-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/f1fb8f6a2e7b/diagnostics-10-00949-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/7697657/c656bc433343/diagnostics-10-00949-g003.jpg

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NEUROD1 is highly expressed in extensive-disease small cell lung cancer and promotes tumor cell migration.
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YAP1 表达与小细胞肺癌的生存和免疫抑制有关。
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