黑色素瘤中程序性细胞死亡表达的转录、生长因子、AKT/mTOR 信号通路成分、受体和配体

K. V. Nikulnikov, V. A. Bogdanova, L. V. Spirina, S. U. Chizhevskaya, I. V. Kondakova, E. Choynzonov, V. I. Chernov
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引用次数: 0

摘要

简介黑色素瘤是最危险的皮肤肿瘤,具有恶性和侵袭性的特点。转录因子和生长因子、AKT/mTOR 信号通路成分、受体和程序性细胞死亡配体参与了肿瘤发生的重要过程。研究皮肤和粘膜肿瘤组织中 AKT/mTOR(mTOR--哺乳动物雷帕霉素靶标)信号通路成分、转录和生长因子、AMPK、LC3B、程序性细胞死亡 1(PD-1)、程序性死亡配体 1 PD-L1 和程序性死亡配体 2(PD-L2)的表达。研究对象包括在托木斯克国立研究医疗中心癌症研究所头颈部肿瘤科接受治疗的21名经确诊为不同部位皮肤和鼻腔粘膜黑色素瘤T1a-4bN0M0(I-IV期)患者和18名不同部位皮肤基底细胞癌T1-4N0M0(I-VIA期)患者,他们的年龄在45至72岁之间。肿瘤溃疡的存在是通过显微镜检查和登记肿瘤上表皮的真正缺失或表皮创伤而确定的。通过实时聚合酶链反应测定肿瘤组织中 AKT/mTOR 信号通路成分、转录因子和生长因子的表达,以及 AMPK、LC3B、PD-1、PD-L1 和 PD-L2 的表达。与基底细胞癌相比,黑色素瘤组织中 70 S6 激酶和 VHL 的表达增加。同时,在缺氧诱导因子 2(HIF-2)转录因子表达增加的背景下,溃疡迹象的存在与低水平的 c-RAF、核因子卡巴 B(NF-kB)p50 和缺氧诱导因子 1(HIF-1)基质 RNA(mRNA)有关。根据布雷斯洛理论对肿瘤分子特征与肿瘤厚度的关系进行的研究显示,转录因子和生长因子、细胞内信号转导过程的强度、微环境的改变、自噬和新血管生成都对肿瘤有影响。黑色素瘤的分子和生物学特征与肿瘤的侵袭性生长有关。70 S6 激酶和 VHL 的表达增加是恶性皮肤肿瘤的特征。溃疡和肿瘤侵袭迹象的出现与诱导关键标志物的因子转录特征的变化有关,肿瘤发生有助于肿瘤侵袭潜能的形成。
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Transcriptional, growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death expression in melanoma
Introduction. Melanoma is the most dangerous neoplasm of the skin, characterized by a malignant and aggressive course. Transcriptional and growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death are involved in significant processes of oncogenesis.Aim. To study the expression of components of the AKT/mTOR (mTOR – mammalian target of rapamycin) signaling pathway, transcription and growth factors, expression of AMPK, LC3B, programmed cell death 1 (PD-1), programmed death-ligand 1 PD-L1 and programmed death-ligand 2 (PD-L2) in skin and mucosal tumor tissues.Materials and methods. The study included 21 patients with a verified diagnosis of melanoma of the skin of various localizations and mucous membranes of the nasal cavity T1a–4bN0M0 (I–IV stages) and 18 patients with basal cell carcinoma of the skin of various localizations T1–4N0M0 (I–VIA stages), aged 45 to 72 years old, who were treated in the department of head and neck tumors of the Cancer Research Institute, Tomsk National Research Medical Center. The presence of tumor ulceration was determined by microscopy and registration of the true absence of the epidermis over the tumor or due to traumatization of the epidermis. Expression of components of the AKT/mTOR signaling pathway, transcription and growth factors, expression of AMPK, LC3B, PD-1, PD-L1 and PD-L2 in the tumor tissue was determined by real-time polymerase chain reaction.Results. An increase in the expression of 70 S6 kinase and VHL was found in melanoma tissues compared to basal cell carcinoma. At the same time, the presence of signs of ulceration was associated with a low level of c-RAF, nuclear factor kappa B (NF-kB) p50 and hypoxia-inducible factor 1 (HIF-1) matrix RNA (mRNA) against the background of an increase in the expression of the hypoxia-inducible factor 2 (HIF-2) transcription factor. The study of the molecular features of neoplasms in relation to the tumor thickness according to Breslow revealed the contribution of transcription and growth factors, the intensity of intracellular signaling processes, modification of the microenvironment, autophagy and neoangiogenesis.Conclusion. The molecular and biological features of melanomas associated with invasive tumor growth have been identified. An increase in the expression of 70 S6 kinase and VHL are characteristic of a malignant skin tumor. The presence of signs of ulceration and tumor invasion were associated with a change in the transcriptional characteristics of factors with the induction of key markers, oncogenesis, which contributes to the formation of the invasive potential of the tumor.
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