Anhui Province Key Laboratory of Biological Macromolecules Research, Wannan Medical College, Wuhu, 241002, China.
Department of Endocrinology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241002, China.
Sci Rep. 2022 Apr 22;12(1):6634. doi: 10.1038/s41598-022-10608-y.
Disintegrin and metalloproteinase 12 (ADAM12) is thought to trigger the occurrence and development of numerous tumours, including colorectal, breast, and pancreatic cancers. On the basis of The Cancer Genome Atlas (TCGA) datasets, in this study, the relationship between ADAM12 gene expression and hepatocellular carcinoma (HCC), the prognostic value of this relationship, and the potential mechanisms influencing HCC development were evaluated. The results showed that the ADAM12 gene was significantly and highly expressed in liver cancer tissue. The high expression of the ADAM12 gene in liver cancer tissue significantly and positively correlated with T stage, pathological stage, and residual tumour. Kaplan-Meier and Cox regression analyses revealed that ADAM12 gene expression is an independent risk factor influencing the prognosis of patients with liver cancer. Pathway analyses of ADAM12 in HCC revealed ADAM12-correlated signalling pathways, and the expression level of ADAM12 was associated with immune cell infiltration. In vitro experiments demonstrated that the expression level of ADAM12 in Huh-7 and Hep3B cells was significantly higher than that in other HCC cells. ShRNA transfection experiments confirmed that the expression levels of TGF-β and Notch pathway-related proteins were significantly decreased. An EdU cell proliferation assay showed that a low level of ADAM12 gene expression significantly inhibited the proliferative activity of HCC cells. Cell cycle experiments showed that low ADAM12 expression blocked the G1/S phase transition. Overall, this research revealed that high ADAM12 gene expression implies a poor prognosis for patients with primary liver cancer. In addition, it is a potential indicator for the diagnosis of liver cancer.
解整合素金属蛋白酶 12（ADAM12）被认为触发了许多肿瘤的发生和发展，包括结直肠癌、乳腺癌和胰腺癌。本研究基于癌症基因组图谱（TCGA）数据集，评估了 ADAM12 基因表达与肝细胞癌（HCC）的关系、这种关系的预后价值以及影响 HCC 发展的潜在机制。结果表明，ADAM12 基因在肝癌组织中显著且高度表达。肝癌组织中 ADAM12 基因的高表达与 T 分期、病理分期和残留肿瘤显著且呈正相关。Kaplan-Meier 和 Cox 回归分析表明，ADAM12 基因表达是影响肝癌患者预后的独立危险因素。HCC 中 ADAM12 的通路分析揭示了 ADAM12 相关信号通路，并且 ADAM12 的表达水平与免疫细胞浸润相关。体外实验表明，Huh-7 和 Hep3B 细胞中 ADAM12 的表达水平明显高于其他 HCC 细胞。shRNA 转染实验证实，TGF-β和 Notch 通路相关蛋白的表达水平显著降低。EdU 细胞增殖实验表明，ADAM12 基因表达水平低显著抑制 HCC 细胞的增殖活性。细胞周期实验表明，低 ADAM12 表达阻止了 G1/S 期转换。总体而言，这项研究表明，ADAM12 基因的高表达意味着原发性肝癌患者的预后不良。此外，它可能是肝癌诊断的潜在指标。
