Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Jiangxi, 330006, Nanchang, China.
J Cancer Res Clin Oncol. 2023 Oct;149(13):11891-11905. doi: 10.1007/s00432-023-05084-4. Epub 2023 Jul 6.
Although some RBM proteins family members play important roles in hepatocellular carcinoma (HCC) development, their value of prognosis and tumor treatment is not clear. To reveal the expression patterns and clinical significance of RBM family members in HCC, we constructed a RBM family-based prognosis signature.
We collected the data of HCC patients from TCGA and ICGC database. The prognostic signature was constructed in TCGA and verified using ICGC cohort. Based on this model, risk score was calculated and patients were divided into high- and low-risk group. Comparison of immune cell infiltration, the response to immunotherapy, and IC50 of chemotherapeutic drugs were employed between different risk subgroups. Besides, CCK-8 and EdU assays were performed to investigate the role of RBM45 in HCC.
Among 19 differential expression RBM protein family genes, 7 prognostic genes were picked out. Through LASSO Cox regression, a 4-gene prognostic model was successfully constructed, which included RBM8A, RBM19, RBM28 and RBM45. Results of validation and estimation suggested this model could be applied for prognostic prediction in HCC patients with a well predictive value. Risk score was shown to be an independent predictor and high-risk patients had poor prognosis. High-risk patients had an immunosuppressive tumor microenvironment while patients with low risk could benefit more from ICI therapy and sorafenib treatment. In addition, knockdown of RBM45 inhibited the proliferation of HCC.
This prognostic signature based on RBM family had a great value for predicting OS of HCC patients. Low-risk patients were more suitable for receiving immunotherapy and sorafenib treatment. The RBM family members made of the prognostic model might promote the progression of HCC.
虽然一些 RBM 蛋白家族成员在肝细胞癌（HCC）发展中发挥重要作用，但它们在预后和肿瘤治疗中的价值尚不清楚。为了揭示 RBM 家族成员在 HCC 中的表达模式和临床意义，我们构建了一个基于 RBM 家族的预后签名。
我们从 TCGA 和 ICGC 数据库中收集 HCC 患者的数据。在 TCGA 中构建预后签名，并在 ICGC 队列中进行验证。基于该模型，计算风险评分并将患者分为高风险组和低风险组。比较不同风险亚组之间的免疫细胞浸润、免疫治疗反应和化疗药物 IC50。此外，通过 CCK-8 和 EdU 测定法研究 RBM45 在 HCC 中的作用。
在 19 个差异表达的 RBM 蛋白家族基因中，筛选出 7 个预后基因。通过 LASSO Cox 回归，成功构建了一个包含 RBM8A、RBM19、RBM28 和 RBM45 的 4 基因预后模型。验证和评估结果表明，该模型可用于 HCC 患者的预后预测，具有良好的预测价值。风险评分是独立的预测因子，高风险患者预后较差。高风险患者的肿瘤微环境具有免疫抑制作用，而低风险患者可能从免疫检查点抑制剂（ICI）治疗和索拉非尼治疗中获益更多。此外，敲低 RBM45 抑制了 HCC 的增殖。
基于 RBM 家族的预后签名对预测 HCC 患者的 OS 具有重要价值。低风险患者更适合接受免疫治疗和索拉非尼治疗。预后模型中的 RBM 家族成员可能促进 HCC 的进展。
