Kosacka Monika, Dyła Tomasz, Chaszczewska-Markowska Monika, Bogunia-Kubik Katarzyna, Brzecka Anna
Department of Pulmonology and Lung Oncology, Wroclaw Medical University, 53439 Wroclaw, Poland.
Laboratory of Clinical Immunogenetics and Pharmacogenetics, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53114 Wroclaw, Poland.
J Clin Med. 2021 Aug 27;10(17):3859. doi: 10.3390/jcm10173859.
Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation.
To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients.
A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV-in 48, stage IIIB-in 33, stage IIIA-in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed.
BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study.
Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease.
肺癌是全球最常见的癌症之一，也是癌症相关死亡的主要原因。骨形态发生蛋白-4（BMP-4）是一种细胞外信号分子，参与许多重要过程，包括细胞增殖与迁移、细胞凋亡和血管生成。血小板反应蛋白-1（TSP-1）属于细胞外基质蛋白。它参与细胞间和细胞与基质间的相互作用，因此在肿瘤微环境中对癌症发展和转移形成起着重要作用。
研究肺癌患者血清中TSP-1和BMP-4水平以及BMP-4基因多态性。
共纳入111例新诊断肺癌患者（76例男性），其中非小细胞肺癌患者102例，小细胞肺癌患者9例。99例（89%）患者诊断为肺癌晚期：IV期48例，IIIB期33例，IIIA期18例；II期6例，I期6例。对照组由61名健康人组成。采用酶联免疫吸附测定法（ELISA）检测所有受试者血清中BMP-4和TSP-1水平。使用实时荧光定量聚合酶链反应（Real-Time PCR）系统对BMP-4进行基因分型。
肺癌患者血清中BMP-4和TSP-1水平显著低于对照组（TSP-1：10109.2±9581 ng/mL vs. 11415.09±9781 ng/mL，P<0.05；BMP-4：138.35±62.59 pg/mL vs. 226.68±135.86 pg/mL，P<0.001）。肺癌患者中，晚期患者TSP-1水平较低（III-IV期为9282.07±4900.78 ng/mL，I-II期为16933.60±6299.02 ng/mL，P<0.05），有淋巴结转移患者低于无淋巴结转移患者（10000.13±9021.41 ng/mL vs. 18497.75±12548.25 ng/mL，P=0.01）。TSP-1和BMP-4血清水平之间无相关性。BMP-4基因多态性不影响研究结果。
TSP-1和BMP-4水平降低可能是肺癌的潜在指标，低TSP-1水平作为疾病晚期标志物具有额外的重要意义。
