Zong Shaoqi, Huang Guokai, Pan Bo, Zhao Shasha, Ling Changquan, Cheng Binbin
Oncology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200043, People's Republic of China.
Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People's Republic of China.
J Hepatocell Carcinoma. 2024 Mar 12;11:525-542. doi: 10.2147/JHC.S454698. eCollection 2024.
Transcatheter arterial chemoembolization (TACE) is commonly used in the treatment of hepatocellular carcinoma (HCC). However, not all patients respond to this treatment. TACE typically leads to hypoxia in the tumor microenvironment. Therefore, we aimed to construct a prognostic model based on hypoxia-related differentially expressed microRNA (miRNAs) in hepatocellular carcinoma (HCC) and to investigate the potential target mRNAs for predicting TACE response.
The hypoxia-related miRNAs (HRMs) were identified in liver cancer cells, then global test was performed to further select the miRNAs which were associated with recurrence and vascular invasion. A prognostic model was constructed based on multivariate Cox regression analysis; qRT-PCR analysis was used to validate the differentially expressed miRNAs in HCC cell lines under hypoxic condition. We further identified the putative target genes of the miRNAs and investigate the relationship between the target genes and TACE response, immune cells infiltration.
We established a HRMs prognostic model for HCC patients, containing two miRNAs (miR-638, miR-501-5p), the patients with high-HRMs score showed worse survival in discovery and validation cohort; qRT-PCR analysis confirmed that these two miRNAs are up-regulated in hepatoma cells under hypoxic condition. Furthermore, four putative target genes of these two miRNAs were identified (ADH1B, CTH, FTCD, RCL1), which were significantly associated with TACE response, immune score, immunosuppressive immune cells infiltration, PDCD1 and CTLA4.
The HCC-HRMs signature may be utilized as a promising prognostic factor and may have implications for guiding TACE and immune therapy.
经动脉化疗栓塞术（TACE）常用于治疗肝细胞癌（HCC）。然而，并非所有患者对该治疗均有反应。TACE通常会导致肿瘤微环境缺氧。因此，我们旨在构建基于肝细胞癌（HCC）中缺氧相关差异表达微小RNA（miRNA）的预后模型，并研究预测TACE反应的潜在靶标mRNA。
在肝癌细胞中鉴定缺氧相关miRNA（HRM），然后进行全局检验以进一步选择与复发和血管侵犯相关的miRNA。基于多变量Cox回归分析构建预后模型；采用qRT-PCR分析验证缺氧条件下HCC细胞系中差异表达的miRNA。我们进一步鉴定了miRNA的假定靶基因，并研究了靶基因与TACE反应、免疫细胞浸润之间的关系。
我们为HCC患者建立了一个HRM预后模型，包含两个miRNA（miR-638、miR-501-5p），高HRM评分的患者在发现和验证队列中的生存率较差；qRT-PCR分析证实这两个miRNA在缺氧条件下的肝癌细胞中上调。此外，鉴定了这两个miRNA的四个假定靶基因（ADH1B、CTH、FTCD、RCL1），它们与TACE反应、免疫评分、免疫抑制性免疫细胞浸润、PDCD1和CTLA4显著相关。
HCC-HRM特征可能作为一种有前景的预后因素，可能对指导TACE和免疫治疗有意义。
