Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases.

IF 4.2 3区 医学 Q2 ONCOLOGY
Clinical & Experimental Metastasis Pub Date : 2024-10-01 Epub Date: 2024-03-29 DOI:10.1007/s10585-024-10279-1
Sophia Leduc, Ha-Linh Nguyen, François Richard, Gitte Zels, Amena Mahdami, Maxim De Schepper, Marion Maetens, Anirudh Pabba, Joris Jaekers, Emily Latacz, Ali Bohlok, Evy Vanderheyden, Thomas Van Brussel, Bram Boeckx, Rogier Schepers, Diether Lambrechts, Luc Dirix, Denis Larsimont, Sophie Vankerckhove, Valerio Lucidi, Baki Topal, Imane Bachir, Vincent Donckier, Giuseppe Floris, Peter Vermeulen, Christine Desmedt
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Abstract

Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.

乳腺癌肝转移组织病理学生长模式的转录组学特征分析
转移性乳腺癌(mBC)仍是不治之症,在所有 mBC 患者中,约 50% 的患者会出现肝转移(LM)。在某些情况下,手术切除乳腺癌肝转移灶(BCLM)可延长患者的生存期。然而,目前还没有有效的标记物来识别这些患者。转移癌细胞与肝脏微环境之间的相互作用导致了两种主要的组织病理学生长模式(HGP):置换型(r-HGP),其特点是癌细胞与肝细胞直接接触;脱瘤型(d-HGP),即肿瘤细胞周围有纤维缘。在接受 BCLM 切除术的患者中,r-HGP 的术后预后比 d-HGP 差。在此,我们旨在揭示在同一转移灶内同时出现两种 HGP 的 10 例患者中,这两种 HGP 之间的生物学差异。转录组分析显示,r-HGP 中涉及细胞周期、DNA 修复、血管增生和细胞运动的基因表达过高,而 d-HGP LM 中血管生成、伤口愈合和几个免疫过程的基因表达过高。了解鳞状上皮细胞的生物学特性可为改进对患有鳞状上皮细胞的巴塞尔公约患者的治疗开辟道路。
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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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