Department of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
J Biochem Mol Toxicol. 2022 Dec;36(12):e23208. doi: 10.1002/jbt.23208. Epub 2022 Sep 6.
A comprehensive analysis of the prognostic, diagnostic, and biological significance of miR-148a-3p and cathepsin A (CTSA) in hepatocellular carcinoma (HCC) was performed using bioinformatics algorithms with The Cancer Genome Atlas (TCGA) data. miR-148a-3p and CTSA gene expression in HCC tissues and nontumor specimens was analyzed using TCGA database with R software. CTSA staining analysis was validated using the Human Protein Atlas database. Prognostic, diagnostic, gene set enrichment, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration analyses were implemented using the TCGA database with R software. Based on TCGA data and our cohort populations, CTSA expression was significantly elevated in HCC tissues compared with nontumor specimens. A significant negative correlation between miR-148a-3p and CTSA was observed in the TCGA data and our cohort population. Mechanistically, CTSA was a direct gene target of miR-148a-3p. Both CTSA and miR-148a-3p could serve as prognostic and diagnostic indicators in HCC. miR-148a-3p expression was significantly and negatively correlated with the StromalScore, ImmuneScore, and ESTIMATEScore in patients with liver cancer. miR-148a-3p mimic-mediated apoptosis and the inhibition of HCC cell growth and migration were counteracted by CTSA overexpression. The miR-148a-3p/CTSA axis was implicated in immune cell infiltration and carcinogenesis of HCC. miR-148a-3p and CTSA might be prospective molecular targets to enhance the potency of immunotherapy in HCC.
使用生物信息学算法和癌症基因组图谱 (TCGA) 数据对 miR-148a-3p 和组织蛋白酶 A (CTSA) 在肝细胞癌 (HCC) 中的预后、诊断和生物学意义进行了全面分析。使用 R 软件分析了 TCGA 数据库中 HCC 组织和非肿瘤标本中的 miR-148a-3p 和 CTSA 基因表达。使用人类蛋白质图谱数据库验证了 CTSA 染色分析。使用 R 软件对 TCGA 数据库进行了预后、诊断、基因集富集、基因本体论、京都基因与基因组百科全书和免疫浸润分析。基于 TCGA 数据和我们的队列人群，与非肿瘤标本相比，HCC 组织中 CTSA 的表达明显升高。在 TCGA 数据和我们的队列人群中观察到 miR-148a-3p 与 CTSA 呈显著负相关。从机制上讲，CTSA 是 miR-148a-3p 的直接靶基因。CTSA 和 miR-148a-3p 均可作为 HCC 的预后和诊断指标。miR-148a-3p 的表达与肝癌患者的基质评分、免疫评分和 ESTIMATEScore 呈显著负相关。CTSA 过表达可拮抗 miR-148a-3p 模拟物介导的细胞凋亡以及 HCC 细胞生长和迁移的抑制作用。miR-148a-3p/CTSA 轴参与 HCC 免疫细胞浸润和发生。miR-148a-3p 和 CTSA 可能是增强 HCC 免疫治疗效力的有前途的分子靶点。
