Oh Sooyeon, Lee Sang-Soo, Jin Hoeyoung, Choi Seo-Hyeon, Cha Choong-Keun, Lee Jooho, Kwack KyuBum, Kim Sang Gyun, Choi Sang-Woon
Chaum Life Center, CHA University School of Medicine, Seoul, 06062, Korea.
Graduate school of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea.
Sci Rep. 2025 Jan 4;15(1):763. doi: 10.1038/s41598-024-84237-y.
No biomarker can effectively screen for early gastric cancer (EGC). Players in the A disintegrin and metalloproteinase (ADAM)-natural killer group 2 member D (NKG2D) receptor axis may have a role for that. As a proof-of-concept pilot study, the expression of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17, and major histocompatibility complex (MHC) class I chain-related sequence A (MICA), a ligand for NKG2D, in gastric cancer was investigated in silico using The Cancer Genome Atlas (TCGA) database. Subsequently, the mRNA and protein expression levels of these markers except ADAM8 were tested in blood samples from patients with EGC and healthy controls. In the TCGA data analyses, EGC tissues (n = 57) expressed significantly higher mRNA levels of ADAM8, ADAM9, ADAM10, ADAM12, and ADAM17 than normal tissues (n = 35) (p < 0.005). In human blood sample analyses, ADAM12 (p = 0.0007), ADAM17 mRNA (p < 0.0001) and ADAM10 (p < 0.001) protein were significantly elevated in patients with EGC (n = 27 for mRNA and n = 25 for protein) compared to the controls (n = 30 for mRNA and n = 26 for protein). Areas under the curves calculated by receiver-operating characteristic analysis for ADAM12, ADAM17 mRNA and ADAM10 protein were 0.7568 (95% confidence interval [CI]: 0.6334 to 0.8802), 0.8062 (95% CI: 0.6889 to 0.9234; p < 0.0001), and 0.8108 (95% CI: 0.6895 to 0.9320; p = 0.0001), respectively. Thus, ADAM12, ADAM17 mRNA and ADAM10 protein levels in peripheral blood could hold potential as biomarkers for screening EGC, and further investigations are required.
没有生物标志物能够有效地筛查早期胃癌（EGC）。解整合素和金属蛋白酶（ADAM）-自然杀伤细胞2族成员D（NKG2D）受体轴中的相关因子可能在此发挥作用。作为一项概念验证性初步研究，我们利用癌症基因组图谱（TCGA）数据库，在计算机上对胃癌中ADAM8、ADAM9、ADAM10、ADAM12、ADAM17以及NKG2D的配体主要组织相容性复合体（MHC）I类链相关序列A（MICA）的表达进行了研究。随后，我们检测了早期胃癌患者和健康对照者血液样本中除ADAM8外这些标志物的mRNA和蛋白质表达水平。在TCGA数据分析中，早期胃癌组织（n = 57）中ADAM8、ADAM9、ADAM10、ADAM12和ADAM17的mRNA水平显著高于正常组织（n = 35）（p < 0.005）。在人体血液样本分析中，与对照组（mRNA组n = 30，蛋白质组n = 26）相比，早期胃癌患者（mRNA组n = 27，蛋白质组n = 25）血液中的ADAM12（p = 0.0007）、ADAM17 mRNA（p < 0.0001）和ADAM10蛋白质（p < 0.001）水平显著升高。通过对ADAM12、ADAM17 mRNA和ADAM10蛋白质进行受试者工作特征分析计算得到的曲线下面积分别为0.7568（95%置信区间[CI]：0.63至0.8802）、0.8062（95%CI：0.6889至0.9234；p < 0.0001）和0.8108（95%CI：0.6895至0.9320；p = 0.0001）。因此，外周血中ADAM12、ADAM17 mRNA和ADAM10蛋白质水平有可能作为筛查早期胃癌的生物标志物，但还需要进一步研究。
