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空间转录组学鉴定泪腺腺样囊性癌细胞特异性表达特征。

Spatial Transcriptomics Identifies Expression Signatures Specific to Lacrimal Gland Adenoid Cystic Carcinoma Cells.

作者信息

Moeyersoms Acadia H M, Gallo Ryan A, Zhang Michelle G, Stathias Vasileios, Maeng Michelle M, Owens Dawn, Abou Khzam Rayan, Sayegh Yoseph, Maza Cynthia, Dubovy Sander R, Tse David T, Pelaez Daniel

机构信息

Dr. Nasser Ibrahim Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

出版信息

Cancers (Basel). 2023 Jun 16;15(12):3211. doi: 10.3390/cancers15123211.

Abstract

Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed by chemoradiation. Even with this radical treatment, the 10-year survival rate for LGACC is 20% given the propensity for recurrence and metastasis. Due to the rarity of LGACC, its pathobiology is not well-understood, leading to difficulties in diagnosis, treatment, and effective management. Here, we integrate bulk RNA sequencing (RNA-seq) and spatial transcriptomics to identify a specific LGACC gene signature that can inform novel targeted therapies. Of the 3499 differentially expressed genes identified by bulk RNA-seq, the results of our spatial transcriptomic analysis reveal 15 upregulated and 12 downregulated genes that specifically arise from LGACC cells, whereas fibroblasts, reactive fibrotic tissue, and nervous and skeletal muscle account for the remaining bulk RNA-seq signature. In light of the analysis, we identified a transitional state cell or stem cell cluster. The results of the pathway analysis identified the upregulation of PI3K-Akt signaling, IL-17 signaling, and multiple other cancer pathways. This study provides insights into the molecular and cellular landscape of LGACC, which can inform new, targeted therapies to improve patient outcomes.

摘要

尽管泪腺原发性肿瘤较为罕见,但腺样囊性癌(ACC)是最常见且致命的泪腺上皮性恶性肿瘤。泪腺腺样囊性癌(LGACC)的传统治疗方法包括摘除眼球及周围眼眶内容物,随后进行放化疗。即便采取这种根治性治疗,鉴于LGACC有复发和转移的倾向,其10年生存率仍为20%。由于LGACC病例罕见,其病理生物学尚未得到充分了解,这给诊断、治疗及有效管理带来了困难。在此,我们整合了批量RNA测序(RNA-seq)和空间转录组学技术,以识别一种特定的LGACC基因特征,为新型靶向治疗提供依据。在批量RNA-seq鉴定出的3499个差异表达基因中,我们的空间转录组分析结果显示,有15个上调基因和12个下调基因 specifically arise from LGACC细胞,而其余批量RNA-seq特征则由成纤维细胞、反应性纤维化组织以及神经和骨骼肌构成。根据分析结果,我们识别出了一种过渡态细胞或干细胞簇。通路分析结果显示PI3K-Akt信号通路、IL-17信号通路以及多种其他癌症通路出现上调。本研究深入揭示了LGACC的分子和细胞格局,可为改善患者预后的新型靶向治疗提供参考。 (注:原文中“specifically arise from”表述有误,可能是“specifically originating from”,但按要求未作修改)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83be/10296284/28bee5a68e87/cancers-15-03211-g001.jpg

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